Leukemic stem cells show the way

The blood-related cancer leukemia was the first disease where human cancer stem cells (CSCs), or leukemic stem cells (LSCs), were isolated. The hematopoietic system is one of the best tissues for investigating cancer stem cells, since the developmental hierarchy of normal blood formation is well defined. Leukemia can now be viewed as aberrant hematopoietic processes initiated by rare leukemic stem cells (LSC) that have maintained or reacquired the capacity for indefinite proliferation through accumulated mutations and/or epigenetic changes. Yet, despite their critical importance, much remains to be learned about the developmental origin of LSC and the mechanisms responsible for their emergence in the course of the disease. This report will review our current knowledge on leukemic stem cell development and finally demonstrate how these discoveries provide a paradigm for identification of Cancer Stem Cell (CSC) from solid tumors.     

Type VII secretion--mycobacteria show the way

Recent evidence shows that mycobacteria have developed novel and specialized secretion systems for the transport of extracellular proteins across their hydrophobic, and highly impermeable, cell wall. Strikingly, mycobacterial genomes encode up to five of these transport systems. Two of these systems, ESX-1 and ESX-5, are involved in virulence - they both affect the cell-to-cell migration of pathogenic mycobacteria. Here, we discuss this novel secretion pathway and consider variants that are present in various Gram-positive bacteria. Given the unique composition of this secretion system, and its general importance, we propose that, in line with the accepted nomenclature, it should be called type VII secretion.     

Paving the way to the future of Amazonia

The fate of the Brazilian Amazon is threatened by a new wave of frontier expansion following new infrastructure commitments worth US$40 bn from the federal Government. In a recent paper, alarming rates of deforestation and forest degradation have been predicted, which could be either pessimistic or optimistic depending on the scale of forest disturbance being considered. A more decisive preventative approach is needed to prevent further impoverishment of both the biota and rural population of Amazonia.     

A fungal sexual revolution: Aspergillus and Penicillium show the way

Fungi have some of the most diverse sex lives in nature, ranging from self-fertility to obligate outcrossing systems with several thousand different sexes, although at least 20% of fungal species have no known sexual stage. However, recent evidence suggests that many supposed 'asexual' species do indeed have the potential to undergo sexual reproduction. Using experimental and genomic findings from Aspergillus and Penicillium species as examples, it is argued that evidence such as the presence and expression of apparently functional sex-related genes, the distribution of mating-type genes, detection of recombination from population genetic analyses, and the discovery of extant sexual cycles reveal an on-going revolution in the understanding of fungal asexuality.     

Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation

Ischemia-reperfusion (I/R) injury associated with liver transplantation remains a serious complication in clinical practice, in spite of several attempts to solve the problem. The present review focuses on the complexity of I/R injury, summarizing conflicting results obtained from the literature about the mechanisms responsible for it. We also review the therapeutic strategies designed in past years to reduce I/R injury, attempting to explain why most of them have not been applied clinically. These strategies include improvements in pharmacological treatments, modifications of University of Wisconsin (UW) preservation solution based on a variety of additives, and gene therapy. Finally, we will consider new potential protective strategies using trimetazidine, 5-amino-4-imidazole carboxamide riboside (AICAR), melatonin, modulators of the renin-angiotensin system (RAS) and the phosphatidylinositol-3-OH kinase (PI3K)-Akt and the p42/p44 extracellular signal-regulated kinases (Erk 1/2) pathway. These strategies have shown promising results for I/R injury but have not been tested in experimental liver transplantation to date. Moreover, we will review ischemic preconditioning, taking into account the recent clinical studies that suggest that this surgical strategy could be appropriate for liver transplantation.     

Ecology of the North Sea: Problems,successes, failures,future needs

After defining ‘ecology’, outlining the basic categories of ecological research and listing examples of modern ecological investigations, this introductory paper focusses on basic considerations; it is, in essence, a programmatic contribution. Research details on the ecology of the North Sea are the subject of the following papers. Theproblems of ecological North Sea research are formidable. Hydrological and biological fluctuations and variabilities are pronounced. Exchange patterns with the Atlantic are complex, and the inputs of rivers and rain defy exact measurement and prediction. Season, weather, climate—and as yet insufficiently known and controlled human-caused impacts—further complicate the situation. All this results in an unusually high degree of uncertainty. New questions and problems arise before the old ones can be answered or solved. Nevertheless, ecological North Sea research has achieved manysuccesses. The North Sea is the most intensively investigated sea area on our planet. Generations of zoologists, botanists and hydrographers — and more recently microbiologists, meteorologists, climatologists, chemists, pathologists and toxicologists — have produced an impressive body of knowledge. Slowly we are beginning to understand the forces that govern energy budgets and balances, material fluxes, and the factors that control and direct ecosystem dynamics. Essential driving forces of ecosystem dynamics result from microbial, especially bacterial, activities. Ecological modelling has paved the way for new theories and insights, and holds promise for progress towards a predictive ecology.Failures and shortcomings include insufficient long-term research, inadequately designed experiments, and misconceptions in environmental protection. Net changes in ecological processes of an heterogeneous and intensely varying environment such as the North Sea can only be comprehended adequately against the background of sustained measurements over decades.Future needs include: more long-term research; and new patterns of management, institutional organization and financial support. Essential breakthroughs in field-work demand more teamwork, in-situ experimentation and surveys from space. Studies on the health status of organisms and ecosystems should receive more attention. Finally, there is need for changes in human behaviour: we must use our insight and willpower to meet the deadly consequences of our self-made scientific-technological evolution by an equally self-made ethical evolution aimed at achieving a re-harmonization with nature.     

A review of mangrove rehabilitation in the Philippines: successes,failures and future prospects

From half a million hectares at the turn of the century, Philippine mangroves have declined to only 120,000 ha while fish/shrimp culture ponds have increased to 232,000 ha. Mangrove replanting programs have thus been popular, from community initiatives (1930s–1950s) to government-sponsored projects (1970s) to large-scale international development assistance programs (1980s to present). Planting costs escalated from less than US$100 to over $500/ha, with half of the latter amount allocated to administration, supervision and project management. Despite heavy funds for massive rehabilitation of mangrove forests over the last two decades, the long-term survival rates of mangroves are generally low at 10–20%. Poor survival can be mainly traced to two factors: inappropriate species and site selection. The favored but unsuitable Rhizophora are planted in sandy substrates of exposed coastlines instead of the natural colonizers Avicennia and Sonneratia. More significantly, planting sites are generally in the lower intertidal to subtidal zones where mangroves do not thrive rather than the optimal middle to upper intertidal levels, for a simple reason. Such ideal sites have long been converted to brackishwater fishponds whereas the former are open access areas with no ownership problems. The issue of pond ownership may be complex and difficult, but such should not outweigh ecological requirements: mangroves should be planted where fishponds are, not on seagrass beds and tidal flats where they never existed. This paper reviews eight mangrove initiatives in the Philippines and evaluates the biophysical and institutional factors behind success or failure. The authors recommend specific protocols (among them pushing for a 4:1 mangrove to pond ratio recommended for a healthy ecosystem) and wider policy directions to make mangrove rehabilitation in the country more effective.     

Past, present and future directions in human genetic susceptibility to tuberculosis

The historical impression that tuberculosis was an inherited disorder has come full circle and substantial evidence now exists of the human genetic contribution to susceptibility to tuberculosis. This evidence has come from several whole-genome linkage scans, and numerous case-control association studies where the candidate genes were derived from the genome screens, animal models and hypotheses pertaining to the disease pathways. Although many of the associated genes have not been validated in all studies, the list of those that have been is growing, and includes NRAMP1, IFNG, NOS2A, MBL, VDR and some TLR . Certain of these genes have consistently been associated with tuberculosis in diverse populations. The future investigation of susceptibility to tuberculosis is almost certain to include genome-wide association studies, admixture mapping and the search for rare variants and epigenetic mechanisms. The genetic identification of more vulnerable individuals is expected to inform personalized treatment and perhaps vaccination strategies.     

Plant breeding: Past achievements and expectations for the future

Plant breeding improvements have been responsible for 50 percent or more of the gains in yield per unit area of major crop plants in the United States over the past 50 yr. Rates of gain attributable to genetic improvements have averaged 1% per year, have generally been linear, and show no sign of slackening. Extrapolations indicate that varieties and hybrids of the year 2000 will yield, on average, 15% more than those of 1985 Improvements in tolerance to environmental stress, in grain-to-straw ratios, and in standability, as well as maintenance of required levels of resistance to disease, insect and nematode pests, have been the major genetic causes of higher achieved yields and will continue to be the foundation for further gains in productivity and stability. Broadened genetic diversity is also an increasingly important goal to promote stability and increase productivity potentials. Proportionately large research inputs are now needed to maintain desired rates of improvement, compared to earlier years. It seems likely that contributions from biotechnology will become increasingly important in years to come if improvement rates are to be maintained.     

Life on the edge: Past and future of mangroves

Wetlands Ecology and Management -     

The impact of alternative splicing in vivo: mouse models show the way

Alternative splicing is widely believed to have a major impact on almost all biological processes since it increases proteome complexity and thereby controls protein function. Recently, gene targeting in mice has been used to create in vivo models to study the regulation and consequences of alternative splicing. The evidence accumulated so far argues for a nonredundant, highly specific role of individual splicing factors in mammalian development, and furthermore, demonstrates the importance of distinct protein isoforms in vivo. In this review, we will compare phenotypes of mouse models for alternative splicing to crystallize common themes and to put them into perspective with the available in vitro data.     

Past, present and future strategies to study the genetics of body weight regulation.

Genetic advances have made remarkable progress towards our understanding of body weight regulation. Much of our current knowledge has come from the cloning and characterisation of the genes responsible for obesity syndromes in the mouse, and the identification of homologous mutations causing rare forms of obesity in humans. Gene targeting experiments in mice have been instrumental in confirming the importance of many genes in the aetiology of obesity, and the existence of a fundamental physiological pathway that controls energy balance is becoming clear. The genetic determinants that underlie common forms of human obesity are largely polygenic, with most genes producing small effects. Thus, elucidating the many genetic determinants of obesity is a current challenge for modern geneticists. Despite the inherent difficulties, progress has been made through linkage/association studies and a genetic map of quantitative trait loci for human obesity is beginning to emerge. Obesity research is now very much in a transition period. Not so long ago, access to high throughput screening, as well as microarray and proteomic techniques, was prohibitively expensive and available only to the few. In recent years, these technologies have become more accessible to the larger scientific community and, in this paper, we will discuss how such technological advances are likely to drive the next wave of progress in obesity research. For example, large-scale mutagenesis screens in rodents coupled with high throughput screening are likely to emerge as important technologies for identifying genes previously unexpected to be involved in body weight regulation. Furthermore, applications of microarray and proteomic techniques will further refine our understanding of currently known peptides as well as identify novel pathways and molecules which are involved in energy homeostasis.     

Classification and identification of the Burkholderia cepacia complex: Past, present and future

The Burkholderia cepacia complex is a group of closely related species with conflicting biological properties. Triggered by the devastating effect of pulmonary infections in cystic fibrosis patients, the scientific community generated an unusually large amount of taxonomic data for these bacteria during the past 15 years. This review presents the polyphasic, multilocus and genomic methodology used for the classification and identification of these bacteria. The current state-of-the-art demonstrates that present day taxonomists can replace traditional DNA-DNA hybridizations for species level demarcation and 16S rRNA sequence analysis for studying phylogeny by superior whole genome sequence-based parameters within the framework of polyphasic taxonomic studies.