The new reconstructive ladder: modifications to the traditional model

The traditional reconstructive ladder has withstood the test of time, serving as a thought paradigm to guide surgeons in choosing their method of wound closure for an assortment of defects. Advances in anatomical understanding and technological innovations have improved our ability to achieve definitive closure in a wide variety of patients. In this article, the older construct is updated to reflect the use of negative-pressure wound therapy and dermal matrices. Perforator flap concepts are also discussed in terms of their inclusion as a rung on the ladder.     

Pleistocene rewilding: an optimistic agenda for twenty-first century conservation

Large vertebrates are strong interactors in food webs, yet they were lost from most ecosystems after the dispersal of modern humans from Africa and Eurasia. We call for restoration of missing ecological functions and evolutionary potential of lost North American megafauna using extant conspecifics and related taxa. We refer to this restoration as Pleistocene rewilding; it is conceived as carefully managed ecosystem manipulations whereby costs and benefits are objectively addressed on a case-by-case and locality-by-locality basis. Pleistocene rewilding would deliberately promote large, long-lived species over pest and weed assemblages, facilitate the persistence and ecological effectiveness of megafauna on a global scale, and broaden the underlying premise of conservation from managing extinction to encompass restoring ecological and evolutionary processes. Pleistocene rewilding can begin immediately with species such as Bolson tortoises and feral horses and continue through the coming decades with elephants and Holarctic lions. Our exemplar taxa would contribute biological, economic, and cultural benefits to North America. Owners of large tracts of private land in the central and western United States could be the first to implement this restoration. Risks of Pleistocene rewilding include the possibility of altered disease ecology and associated human health implications, as well as unexpected ecological and sociopolitical consequences of reintroductions. Establishment of programs to monitor suites of species interactions and their consequences for biodiversity and ecosystem health will be a significant challenge. Secure fencing would be a major economic cost, and social challenges will include acceptance of predation as an overriding natural process and the incorporation of pre-Columbian ecological frameworks into conservation strategies.     

The global nitrogen cycle in the twenty-first century

Global nitrogen fixation contributes 413 Tg of reactive nitrogen (N_r) to terrestrial and marine ecosystems annually of which anthropogenic activities are responsible for half, 210 Tg N. The majority of the transformations of anthropogenic N_r are on land (240 Tg N yr⁻¹) within soils and vegetation where reduced N_r contributes most of the input through the use of fertilizer nitrogen in agriculture. Leakages from the use of fertilizer N_r contribute to nitrate (NO₃⁻) in drainage waters from agricultural land and emissions of trace N_r compounds to the atmosphere. Emissions, mainly of ammonia (NH₃) from land together with combustion related emissions of nitrogen oxides (NO_x), contribute 100 Tg N yr⁻¹ to the atmosphere, which are transported between countries and processed within the atmosphere, generating secondary pollutants, including ozone and other photochemical oxidants and aerosols, especially ammonium nitrate (NH₄NO₃) and ammonium sulfate (NH₄)₂SO₄. Leaching and riverine transport of NO₃ contribute 40–70 Tg N yr⁻¹ to coastal waters and the open ocean, which together with the 30 Tg input to oceans from atmospheric deposition combine with marine biological nitrogen fixation (140 Tg N yr⁻¹) to double the ocean processing of N_r. Some of the marine N_r is buried in sediments, the remainder being denitrified back to the atmosphere as N₂ or N₂O. The marine processing is of a similar magnitude to that in terrestrial soils and vegetation, but has a larger fraction of natural origin. The lifetime of N_r in the atmosphere, with the exception of N₂O, is only a few weeks, while in terrestrial ecosystems, with the exception of peatlands (where it can be 10²–10³ years), the lifetime is a few decades. In the ocean, the lifetime of N_r is less well known but seems to be longer than in terrestrial ecosystems and may represent an important long-term source of N₂O that will respond very slowly to control measures on the sources of N_r from which it is produced.     

Zebrafish: as an integrative model for twenty-first century toxicity testing

The zebrafish embryo is a useful small model for investigating vertebrate development because of its transparency, low cost, transgenic and morpholino capabilities, conservation of cell signaling, and concordance with mammalian developmental phenotypes. From these advantages, the zebrafish embryo has been considered as an alternative model for traditional in vivo developmental toxicity screening. The use of this organism in conjunction with traditional in vivo developmental toxicity testing has the potential to reduce cost and increase throughput of testing the chemical universe, prioritize chemicals for targeted toxicity testing, generate predictive models of developmental toxicants, and elucidate mechanisms and adverse outcome pathways for abnormal development. This review gives an overview of the zebrafish embryo for pre dictive toxicology and 21st century toxicity testing. Developmental eye defects were selected as an example to evaluate data from the U.S. Environmental Protection Agency's ToxCast program comparing responses in zebrafish embryos with those from pregnant rats and rabbits for a subset of 24 environmental chemicals across >600 in vitro assay targets. Cross-species comparisons implied a common basis for biological pathways associated with neuronal defects, extracellular matrix remodeling, and mitotic arrest.     

Plants and human health in the twenty-first century

The concept of growing crops for health rather than for food or fiber is slowly changing plant biotechnology and medicine. Rediscovery of the connection between plants and health is responsible for launching a new generation of botanical therapeutics that include plant-derived pharmaceuticals, multicomponent botanical drugs, dietary supplements, functional foods and plant-produced recombinant proteins. Many of these products will soon complement conventional pharmaceuticals in the treatment, prevention and diagnosis of diseases, while at the same time adding value to agriculture. Such complementation can be accelerated by developing better tools for the efficient exploration of diverse and mutually interacting arrays of phytochemicals and for the manipulation of the plant's ability to synthesize natural products and complex proteins. This review discusses the history, future, scientific background and regulatory issues related to botanical therapeutics.     

The effect of development on the direction of evolution: toward a twenty-first century consensus

Summary One of the most important questions in evolutionary biology is: what orients the evolutionary process? That is, what causes evolution to proceed toward certain developmental trajectories, and hence phenotypes, rather than others? In particular, there has been prolonged controversy over whether the direction of evolution is determined solely by external factors or whether the nature of the ontogenetic process, and the ways in which it can be altered by mutations in developmental genes, may also play a major role. Here, I examine this issue, concentrating on the following: the possible evolutionary orienting role of “developmental bias;” the question of whether selection can and/or will break bias; the extent to which bias is already incorporated in quantitative genetic studies; and ways of approaching the possible role of bias in the origin of evolutionary novelties. Finally, I suggest that developmental bias may provide a focal point for the coming together of conceptual and practical approaches to evo‐devo.     

Making a difference--women, medicine, and the twenty-first century

Women can and should make a difference in how medical care is given in the future. The increased number of women physicians presents an opportunity to make a significant impact on the quality of medical care. Data is provided on the number of women applicants to medical school, matriculants and graduates, specialty choices, the status of women in academic medicine, and the income of women physicians. Four aspects of the environment that portend important changes for medicine in the future are identified: scientific developments, alternative delivery systems and the corporate practice of medicine, the aging population and other demographic changes, and the expanding number of physicians. Some of these changes suggest opportunities for making a difference in the traditional specialties of medicine, in providing care to underserved populations, in research careers, in the shortage areas of preventive medicine and public health, occupational medicine, child psychiatry, and physical medicine and rehabilitation, and in new areas such as community pediatrics, behavioral pediatrics, and adolescent medicine. There are many choices and many decisions to be made, and each individual can choose to make a difference.     

Biological systems modeling and analysis: a biomolecular technique of the twenty-first century.

It is proposed that computational systems biology should be considered a biomolecular technique of the twenty-first century, because it complements experimental biology and bioinformatics in unique ways that will eventually lead to insights and a depth of understanding not achievable without systems approaches. This article begins with a summary of traditional and novel modeling techniques. In the second part, it proposes concept map modeling as a useful link between experimental biology and biological systems modeling and analysis. Concept map modeling requires the collaboration between biologist and modeler. The biologist designs a regulated connectivity diagram of processes comprising a biological system and also provides semi-quantitative information on stimuli and measured or expected responses of the system. The modeler converts this information through methods of forward and inverse modeling into a mathematical construct that can be used for simulations and to generate and test new hypotheses. The biologist and the modeler collaboratively interpret the results and devise improved concept maps. The third part of the article describes software, BST-Box, supporting the various modeling activities.     

Elucidating the ticking of an in vitro circadian clockwork

A biochemical oscillator can be reconstituted in vitro with three purified proteins, that displays the salient properties of circadian (daily) rhythms, including self-sustained 24-h periodicity that is temperature compensated. We analyze the biochemical basis of this oscillator by quantifying the time-dependent interactions of the three proteins (KaiA, KaiB, and KaiC) by electron microscopy and native gel electrophoresis to elucidate the timing of the formation of complexes among the Kai proteins. The data are used to derive a dynamic model for the in vitro oscillator that accurately reproduces the rhythms of KaiABC complexes and of KaiC phosphorylation, and is consistent with biophysical observations of individual Kai protein interactions. We use fluorescence resonance energy transfer (FRET) to confirm that monomer exchange among KaiC hexamers occurs. The model demonstrates that the function of this monomer exchange may be to maintain synchrony among the KaiC hexamers in the reaction, thereby sustaining a high-amplitude oscillation. Finally, we apply the first perturbation analyses of an in vitro oscillator by using temperature pulses to reset the phase of the KaiABC oscillator, thereby testing the resetting characteristics of this unique circadian oscillator. This study analyzes a circadian clockwork to an unprecedented level of molecular detail.