Recent progress in expanding the chemiluminescent toolbox for bioimaging

1. Download : Download high-res image (226KB)
2. Download : Download full-size image

     

Emerging strategies for expanding the toolbox of enzymes in biocatalysis

Expanding the repertoire of reactions available to enzymes is an enduring challenge in biocatalysis. Owing to the synthetic versatility of transition metals, metalloenzymes have been favored targets for achieving new catalytic functions. Although less well explored, enzymes lacking metal centers can also be effective catalysts for non-natural reactions, providing access to reaction modalities that compliment those available to metals. By understanding how these activation modes can reveal new functions, strategies can be developed to access novel biocatalytic reactions. This review will cover discoveries in the last two years which access catalytic reactions that go beyond the native repertoire of metal-free biocatalysts.     

Biological challenges to effective vaccines in the developing world

The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy.     

Using DNA barcoding to assess Caribbean reef fish biodiversity: expanding taxonomic and geographic coverage

This paper represents a DNA barcode data release for 3,400 specimens representing 521 species of fishes from 6 areas across the Caribbean and western central Atlantic regions (FAO Region 31). Merged with our prior published data, the combined efforts result in 3,964 specimens representing 572 species of marine fishes and constitute one of the most comprehensive DNA barcoding "coverages" for a region reported to date. The barcode data are providing new insights into Caribbean shorefish diversity, allowing for more and more accurate DNA-based identifications of larvae, juveniles, and unknown specimens. Examples are given correcting previous work that was erroneous due to database incompleteness.     

Defining standard of care in the developing world: the intersection of international research ethics and health systems analysis

In recent years there has been intense debate regarding the level of medical care provided to 'standard care' control groups in clinical trials in developing countries, particularly when the research sponsors come from wealthier countries. The debate revolves around the issue of how to define a standard of medical care in a country in which many people are not receiving the best methods of medical care available in other settings. In this paper, we argue that additional dimensions of the standard of care have been hitherto neglected, namely, the structure and efficiency of the national health system. The health system affects locally available medical care in two important ways: first, the system may be structured to provide different levels of care at different sites with referral mechanisms to direct patients to the appropriate level of care. Second, inefficiencies in this system may influence what care is available in a particular locale. As a result of these two factors locally available care cannot be equated with a national 'standard'. A reasonable approach is to define the national standard of care as the level of care that ought to be delivered under conditions of appropriate and efficient referral in a national system. This standard is the minimum level of care that ought to be provided to a control group. There may be additional moral arguments for higher levels of care in some circumstances. This health system analysis may be helpful to researchers and ethics committees in designing and reviewing research involving standard care control groups in developing country research.     

Growth and mortality in mountain hares: the effect of sex and date of birth

Summary Current theory suggests that high juvenile growth effort, may result in higher mortality. This prediction is tested in mountain hares (Lepus timidus), by examination of post-weaning growth and mortality of males and females. Dates of birth were estimated from weight at first capture and growth in body weight and hind foot length was described by the logistic growth equation. Although adult female hares are on average larger than males, this results from a longer period of growth and not from a faster growth rate. There was no clear sex bias in mortality, a slight but not significantly greater proportion of males suffered mortality during the growth period. Predictions as to sex difference in mortality should specify which aspects of growth (rate or duration) are the agents of mortality, since the two parameters are not necessarily positively associated. Overall asymptotic body size decreased and rate of growth increased from early through to late-born young. Rate of growth in hind foot length was greater in late-born males but not in late-born females as compared with those born earlier. It is hypothesized that late-born males are more tightly constrained to complete growth and subsequent sexual maturation earlier than late-born females.     

Gene duplication and other evolutionary strategies: from the RNA world to the future

Beginning with a hypothetical RNA world, it is apparent that many evolutionary transitions led to the complexity of extant species. The duplication of genetic material is rooted in the RNA world. One of two major routes of gene amplification, retroposition, originated from mechanisms that facilitated the transition to DNA as hereditary material. Even in modern genomes the process of retroposition leads to genetic novelties including the duplication of protein and RNA coding genes, as well as regulatory elements and their juxtapositon. We examine whether and to what extent known evolutionary principles can be applied to an RNA-based world. We conclude that the major basic Neo-Darwinian principles that include amplification, variation and selection already governed evolution in the RNA and RNP worlds. In this hypothetical RNA world there were few restrictions on the exchange of genetic material and principles that acted as borders at later stages, such as Weismann's Barrier, the Central Dogma of Molecular Biology, or the Darwinian Threshold were absent or rudimentary. RNA was more than a gene: it had a dual role harboring, genotypic and phenotypic capabilities, often in the same molecule. Nuons, any discrete nucleic acid sequences, were selected on an individual basis as well as in groups. The performance and success of an individual nuon was markedly dependent on the type of other nuons in a given cell. In the RNA world the transition may already have begun towards the linkage of nuons to yield a composite linear RNA genome, an arrangement necessitating the origin of RNA processing. A concatenated genome may have curbed unlimited exchange of genetic material; concomitantly, selfish nuons were more difficult to purge. A linked genome may also have constituted the beginning of the phenotype/genotype separation. This division of tasks was expanded when templated protein biosynthesis led to the RNP world, and more so when DNA took over as genetic material. The aforementioned barriers and thresholds increased and the significance and extent of horizontal gene transfer fluctuated over major evolutionary transitions. At the dawn of the most recent transformation, a fast evolutionary transition that we will be witnessing in our life times, a form of Lamarckism is raising its head.     

Rights of and duties to non-consenting patients--informed refusal in the developing world

The principle of informed refusal poses a specific problem when it is invoked by a pregnant woman who, in spite of having accepted her pregnancy, refuses the diagnostic and/or therapeutic measures that would ensure the well-being of her endangered fetus. Guidelines issued by professional bodies in the developed world are conflicting: either they allow autonomy and informed consent to be overruled to the benefit of the fetus, or they recommend the full respect of these principles. A number of medical ethicists advocate the overruling of alleged irrational or unreasonable refusal for the benefit of the fetus. The present essay supports the view of fetal rights to health and to life based on the principle that an 'accepted' fetus is a 'third person'. In developing countries, however, the implementation of the latter principle is likely to be in conflict with a 'communitarian' perception of the individual -- in this case, the pregnant woman. Within the scope of the limitations to the right to autonomy of J.S. Mill's 'harm principle', the South African Patients' Charter makes provision for informed refusal. The fact that, in practice, it is not implemented illustrates the well-known difficulty of applying Western bioethical principles in real life in the developing world.     

The next steps for genomic medicine: challenges and opportunities for the developing world

This is a historical moment on the path to genomic medicine - the point at which theory is about to be translated into practice. We have previously described human genome variation studies taking place in Mexico, India, Thailand, and South Africa. Such investments into science and technology will enable these countries to embark on the path to the medical and health applications of genomics, and to benefit economically. Here we provide a perspective on the challenges and opportunities facing these and other countries in the developing world as they begin to harness genomics for the benefit of their populations.