Estrogen and memory in women: how can we reconcile the findings?

Although several randomized controlled trials (RCTS) of surgically menopausal women have provided evidence that estrogen protects aspects of memory, many cross-sectional and longitudinal studies, including those from the RCT, the Women's Health Initiative Memory Study (WHIMS), have reported inconsistent information with regard to the relationship between estrogen and aspects of cognitive function. Although numerous reasons could be offered to explain these discrepancies in research findings, recent evidence from rodent, nonhuman primate, and human studies consistently suggests that one possibility may be critical to our understanding of the estrogenic effect on memory. Results of these animal and human studies indicate that the initiation of estrogen treatment at the time of menopause, or soon after ovariectomy (OVX), provides a window of opportunity for the preservation of memory in females whereas the administration of the hormone following a considerable delay in time after OVX has little or no beneficial effect on cognition. Considering the evidence that, in several organ systems, heightened disease risks accrue to a longer duration of estrogen deprivation in women, it would seem important to determine whether this is also true for brain structure and function in order to protect the quality of life for the considerable number of women who undergo a surgical menopause before their natural menopause had occurred.     

How can we deliver the large plant genomes? Strategies and perspectives

The first sequenced plant genome, from the small mustard plant Arabidopsis thaliana, was published at the end of 2000. The sequencing of the rice genome is well under way. The sizes of plant genomes vary by a factor of up to 1000, and many important crop plants have genomes that are several times larger than the human genome. To gain insight into the gene toolbox of plant species, numerous large-scale EST sequencing projects have been launched successfully, and analysis procedures are constantly being refined to add maximum value to the sequence data. In addition, an alternative approach to exclude repetitive noncoding DNA and to enrich sequence libraries for gene-containing genomic regions has been developed. This strategy has the potential to deliver information about both genes and regulatory regions outside the transcribed regions.     

How can we improve information delivery to support conservation and restoration decisions?

Incorporating science into resource conservation and management is becoming increasingly important, but it is not yet clear how to provide information to decision makers most effectively. To evaluate sources of information used to support the management and conservation of California’s riparian bird habitat, we distributed a questionnaire to restoration practitioners and public and private land managers. We asked respondents to rate the importance and availability of different sources of information they use to inform their decisions. Synthetic reviews and peer-reviewed publications both received high importance and availability ratings. Web-based tools received low importance and availability ratings. One-on-one interactions between ecologists and decision makers received high importance ratings, similar to those of peer-reviewed publications and synthetic reviews, but their availability was rated lower than any other method of decision support. Our results suggest that the decision makers we surveyed are already using a wide variety of information, but that prioritizing one-on-one interactions between scientists and decision makers will enhance the delivery of all sources of information.     

Fight or learn to live with the consequences?

Individuals can fight their infectious diseases by reducing the growth of a pathogen (resistance), but they can also ameliorate the disease it causes (tolerance). A recent paper shows that there is variation between mouse strains in tolerance to a rodent malaria and that this was negatively correlated with resistance. This is important, because tolerance has major implications for the epidemiology and coevolution of host-parasite interactions, but has been neglected in the animal literature.     

How can we possibly resolve the planet's nitrogen dilemma?

Nitrogen is the most crucial element in the production of nutritious feeds and foods. The production of reactive nitrogen by means of fossil fuel has thus far been able to guarantee the protein supply for the world population. Yet, the production and massive use of fertilizer nitrogen constitute a major threat in terms of environmental health and sustainability. It is crucial to promote consumer acceptance and awareness towards proteins produced by highly effective microorganisms, and their potential to replace proteins obtained with poor nitrogen efficiencies from plants and animals. The fact that reactive fertilizer nitrogen, produced by the Haber Bosch process, consumes a significant amount of fossil fuel worldwide is of concern. Moreover, recently, the prices of fossil fuels have increased the cost of reactive nitrogen by a factor of 3 to 5 times, while international policies are fostering the transition towards a more sustainable agro-ecology by reducing mineral fertilizers inputs and increasing organic farming. The combination of these pressures and challenges opens opportunities to use the reactive nitrogen nutrient more carefully. Time has come to effectively recover used nitrogen from secondary resources and to upgrade it to a legal status of fertilizer. Organic nitrogen is a slow-release fertilizer, it has a factor of 2.5 or higher economic value per unit nitrogen as fertilizer and thus adequate technologies to produce it, for instance by implementing photobiological processes, are promising. Finally, it appears wise to start the integration in our overall feed and food supply chains of the exceptional potential of biological nitrogen fixation. Nitrogen produced by the nitrogenase enzyme, either in the soil or in novel biotechnology reactor systems, deserves to have a ‘renaissance’ in the context of planetary governance in general and the increasing number of people who desire to be fed in a sustainable way in particular.     

Resistance to xenobiotics and parasites: can we count the cost?

The nature and cost of single genes of major effect is one of the longest running controversies in biology. Resistance, whether to xenobiotics or to parasites, is often paraded as an obvious example of a single gene effect that must carry an associated fitness 'cost'. However, a review of the xenobiotic resistance literature shows that empirical evidence for this hypothesis is, in fact, scarce. We postulate that such fitness costs can only be fully interpreted in the light of the molecular mutations that might underlie them. We also derive a theoretical framework both to encompass our current understanding of xenobiotic resistance and to begin to dissect the probable cost of parasite resistance.     

Could we live with reintroduced large carnivores in the UK?

1. Literature on the wolf Canis lupus, brown bear Ursus arctos and lynx Lynx lynx is reviewed to determine if sufficient semi‐natural habitat exists in the UK for a viable population of any of these species and to assess the potential risks to human safety, livestock and economically valuable wildlife. Public attitudes to the recovery and reintroduction of some other mammals are also briefly reviewed. 2. The large home range sizes and low population densities of large carnivores mean that the Scottish Highlands is the only UK region with the potential to support a viable population. Human population density is also lower in the Highlands and the density of wild ungulate prey higher than in many parts of Europe where large carnivores survive. 3. Attacks on people have been recorded in Europe for healthy bears and for rabid bears and wolves but there are no reports of attacks by lynx. Bears are more carnivorous in the north of their range than in the south and although wild mammals seldom appear to be important prey serious predation of livestock can occur. Livestock predation is also reported for the wolf and the lynx but they appear to prefer wild prey if available. However, mass kills of up to 100 or more sheep are occasionally recorded for wolves. 4. Attitudes to reintroductions and carnivores generally tend to be favourable amongst the general public, but negative amongst those most likely to be adversely affected. Fears for human safety and significant livestock predation with bears and wolves, respectively, suggest that reintroduction of these species is unlikely to be acceptable in the foreseeable future. Reintroduction of the lynx may be feasible but habitat suitability and potential impact on vulnerable native wildlife need to be assessed. Socio‐economic and legal issues also need to be addressed before such a reintroduction is considered.     

DNA polymerases and SOS mutagenesis: can one reconcile the biochemical and genetic data?

Until recently, it had been concluded from genetic evidence that DNA polymerase III (Pol III, the main replicative polymerase in E. coli) was also responsible for mutagenic translesion synthesis on damaged templates, albeit under the influence of inducible proteins UmuD' and UmuC. Now it appears that these proteins themselves have polymerase activity (and are now known as Pol V) and can carry out translesion synthesis in vitro in the absence of Pol III. Here I discuss the apparent contradictions between genetics and biochemistry with regard to the role of Pol III in translesion synthesis. Does Pol V interact with Pol III and constitute an alternative component of the replication factory (replisome)? Where do the other three known polymerases fit in? What devices does the cell have to ensure that the "right" polymerase is used in a given situation? The debate about the role of Pol III in translesion synthesis reveals a deeper divide between models that interpret everything in terms of mass action effects and those that embrace a replisome held together by protein-protein interactions and located as a structural entity within the cell.     

How can immunology contribute to the control of tuberculosis?

Tuberculosis poses a significant threat to mankind. Multidrug-resistant strains are on the rise, and Mycobacterium tuberculosis infection is often associated with human immunodeficiency virus infection. Satisfactory control of tuberculosis can only be achieved using a highly efficacious vaccine. Tuberculosis is particularly challenging for the immune system. The intracellular location of the pathogen shields it from antibodies, and a variety of T-cell subpopulations must be activated to challenge the bacterium's resistance to antibacterial defence mechanisms. A clear understanding of the immune responses that control the pathogen will be important for achieving optimal immunity, and information provided by functional genome analysis of M. tuberculosis will be vital in the design of a future vaccine.