Chronomodulated chemotherapy and irradiation: an idea whose time has come?

The chronomodulated delivery of systemic chemotherapy given with irradiation (chemoradiation) is driven by an understanding of: the chronobiology of normal tissue response to cytotoxic insult, chronopharmacology, and by technologic advances in vascular access and in the availability of portable programmable pumps. Since circadian variation exists in the proliferative activity of acute-reacting normal tissues like the gut and bone marrow, a potential therapeutic gain can be realized by the chronomodulated administration of S-phase chemotherapeutic agents at biological times when these normal tissues are in a different cell phase and thus relatively spared (chronotolerance). The reasons for this are complex and possibly include newly described time-keeping genes that may influence the cell cycle. Another important aspect of chronotolerance is based on chronopharmacologic behavior of S-phase chemotherapeutic radiation sensitizing agents, especially 5-fluorouracil (5-FU). In this review laboratory and clinical evidence is presented for using chronomodulated 5-FU or the topoisomerase-I inhibitor, camptothecin, when best tolerated biologically. Although the main body of this work has been accomplished with pure chemotherapy schedules, there is emerging clinical evidence this approach to treatment also applies to the application of chemoradiation. This knowledge has been exploited only recently in the clinic. These data should be viewed as a call for additional studies to investigate the precise timing of systemic chemotherapeutic radio sensitizers to ameliorate toxicity and maximize treatment effect, especially with newer and potentially more toxic chemoradiation programs.     

Ecological engineering - An idea whose time has come?

The era of cheap fossil fuels is nearing its end. industrial, agricultural and human pollutants have reached alarming levels in water, soil, air and stratosphere. Consumers no longer tolerate poisons in their food and water, are now concerned with global warming and ozone depletion, and value fields and forests for their scenery and wildlife as well as food and fibre. We are at the crossroads, searching for answers to these and many other pressing ecological problems. On one side sit 'deep ecologists' who patiently await the reactions of global Gaia. On the other sit 'biotechnologists' who would design and build new organisms and new ecosystems. The first approach is defeatist, for it awaits the decimation of the human population. The otheris activist, but will it work? Here we examine the idea of 'ecological engineering', which offers some promise of solutions to our problems if it can integrate the practical sides of ecosystem, landscape, community and population ecology with relevant formal concepts from the engineering sciences.     

Cardiovascular disease in systemic lupus erythematosus: has the time for action come?

PURPOSE OF REVIEW: The recognition that inflammation is a hallmark of atherosclerotic disease has led to a series of studies reporting accelerated atherogenesis in chronic inflammatory diseases. Indeed, systemic lupus erythematosus is associated with an increased incidence of cardiovascular disease and the etiology thereof deserves closer attention. RECENT FINDINGS: The association between systemic lupus erythematosus and accelerated atherosclerosis has recently been confirmed by surrogate-marker studies for cardiovascular disease in patients with systemic lupus erythematosus. Since the propensity towards cardiovascular disease cannot solely be explained by classical risk factors, disease-specific pathways have been put forward as additional risk factors. SUMMARY: In the present review, we will discuss several of these factors as well as their potential impact for future prevention strategies in systemic lupus erythematosus.     

15 years of microbial biotechnology: the time has come to think big—and act soon

Our epoch is largely characterized by the growing realization and concern about the reality of climate change and environmental deterioration, the surge of global pandemics, the unacceptable inequalities between developed and underdeveloped countries and their unavoidable translation into messy immigration, overpopulation and food crises. While all of these issues have a fundamentally political core, they are not altogether removed from the fact that Earth is primarily a microbial planet and microorganisms are the key agents that make the biosphere (including ourselves) function as it does. It thus makes sense that we bring the microbial world—that is the environmental microbiome—to the necessary multi-tiered conversation (hopefully followed by action) on how to avoid future threats and how to make our globe a habitable common house. Beyond discussion on governance, such a dialogue has technical and scientific aspects that only frontline microbial biotechnology can help to tackle. Fortunately, the field has witnessed the onset of new conceptual and material tools that were missing when the journal started.     

Evolution: have wings come,gone and come again?

Can complex traits be re-evolved by lineages that have lost them? Phylogenetic study now suggests that wings may indeed have reappeared several times within the ancestrally wingless stick insects.     

Biogas from Macroalgae: is it time to revisit the idea?

The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example.     

Rapoport's rule: time for an epitaph?

The christening of the decline in the geographic extent of species from high to low latitudes as Rapoport's rule was a bold step. Allowing for a variety of potentially significant complications to the interpretation of empirical studies, evidence that this is indeed a general pattern is, at the very least, equivocal. The present taxonomically and regionally biased set of studies lend support to the recent suggestion that the pattern is a local phenomenon being expressed primarily in the Palaearctic and Nearctic above latitudes of 40-50°N. Five hypotheses have been proposed to explain the generation of latitudinal declines in range size where they do occur, with the past heavy emphasis on a climatic variability mechanism being eroded. Evidence is accruing in support of more than one such mechanism. Whatever the generality of the `rule', it has undoubtedly served to stimulate a consideration of the role of spatial variation in range sizes in several areas of research in ecology and evolution.     

Proximate and ultimate causes: how come? and what for?

Proximate and ultimate causes in evolutionary biology have come to conflate two distinctions. The first is a distinction between immediate and historical causes. The second is between explanations of mechanism and adaptive function. Mayr emphasized the first distinction but many evolutionary biologists use proximate and ultimate causes to refer to the second. I recommend that ‘ultimate cause’ be abandoned as ambiguous.     

The Arabidopsis clock: time for an about-face?

Three recent studies have altered thinking on the role of TIMING OF CAB EXPRESSION 1 (TOC1), a core element in the plant circadian oscillator.