Emergency relocation of a Purple Copper Butterfly colony during roadworks: Successes and lessons learned

Summary  In 2004, the Roads and Traffic Authority (RTA) undertook a road realignment project near Lidsdale in the Central Tablelands of New South Wales. However, the RTA had not detected a population of the threatened Purple Copper Butterfly within the footprint of the project. The RTA responded promptly when notified of the butterflies' presence by stopping works, and preparing and implementing a butterfly management programme. This programme included modifying the realignment (and reducing the development footprint), supplementary planting of habitat, habitat rehabilitation and translocation of individual caterpillars from within the final footprint area. These actions seem to have safeguarded the population at least in the short term; however, further active management of the site will be needed to ensure its long-term viability. The project reinforces the importance of thorough predisturbance assessment of a site at the early planning stages, and the results and observations could be particularly informative in planning for introduction, reintroduction and translocation proposals involving the Purple Copper Butterfly.     

Development and cancer: lessons learned in the pancreas

Cancer progression and organ development are similar phenomena. Both involve rapid bursts of proliferation, angiogenesis, tissue remodeling, and cell migration. Therefore, it is not surprising that both processes utilize similar signaling machinery. In fact, many recent studies have suggested that cancer is a disease triggered by the erroneous re-activation of signaling pathways that are typically downregulated after the completion of embryonic development. This link between embryonic development and cancer is particularly exciting because it suggests that we might be able to exploit the knowledge gained in studies of Developmental Biology to obtain novel insights into tumor biology. Our evolving understanding of pancreatic adenocarcinoma is an excellent example of this relationship between development and cancer. Here we discuss recent studies have indicated important roles for two major developmental signaling pathways in pancreatic cancer: Notch and Hedgehog (Hh).     

The transition from bench to bedside: lessons learned in the creation of a new T-cell product for the clinic

While the technology of translational research is sometimes considered a poor relation to 'basic science', it has become a central focus of work to turn exciting new concepts into practical therapies. Here we use the example of selective T-cell depletion of allografted lymphocytes to illustrate the problems of scale-up, reproducibility, sterility, safety and regulatory concerns encountered during the bench to bedside process.     

Protein name tagging guidelines: lessons learned

Interest in information extraction from the biomedical literature is motivated by the need to speed up the creation of structured databases representing the latest scientific knowledge about specific objects, such as proteins and genes. This paper addresses the issue of a lack of standard definition of the problem of protein name tagging. We describe the lessons learned in developing a set of guidelines and present the first set of inter-coder results, viewed as an upper bound on system performance. Problems coders face include: (a) the ambiguity of names that can refer to either genes or proteins; (b) the difficulty of getting the exact extents of long protein names; and (c) the complexity of the guidelines. These problems have been addressed in two ways: (a) defining the tagging targets as protein named entities used in the literature to describe proteins or protein-associated or -related objects, such as domains, pathways, expression or genes, and (b) using two types of tags, protein tags and long-form tags, with the latter being used to optionally extend the boundaries of the protein tag when the name boundary is difficult to determine. Inter-coder consistency across three annotators on protein tags on 300 MEDLINE abstracts is 0.868 F-measure. The guidelines and annotated datasets, along with automatic tools, are available for research use.     

VTEC: lessons learned from British outbreaks

Important Escherichia coli O157 outbreaks in England and Scotland since 1982-83 are reviewed. The scientific lessons learned from them are described and their legal consequences outlined. The light shed by them on relationships between law and science is discussed, and questions of blame are analysed in the context of Reason's 'resident pathogen' metaphor and Vaughan's study of the 1986 Challenger Space Shuttle disaster.     

Clinical trials in systemic sclerosis: lessons learned and outcomes

The pathogenesis of systemic sclerosis (SSc) is complex and largely unclear. The clinical heterogeneity of the disease and its progression over a number of years makes the choice of endpoints in the design of clinical trials difficult. The overwhelming need in this disease is to diagnose it early and identify those patients who will benefit most from early, aggressive treatment that potentially can alter the clinical disease course. To achieve this, innumerable challenges must be overcome. This article reviews data from recent clinical trials and the lessons derived from retrospective observational studies, databases, and patient registries. Taken together, these observations will help to improve our understanding of the diverse clinical course of SSc and permit refinement of existing outcome measures for the design of future clinical trials, in which the likelihood of observing a positive treatment effect with the drugs at our disposal will be maximized.     

Extensive Sequencing of the CFTR gene: lessons learned from the first 157 patient samples

Cystic fibrosis (CF) is one of the most common monogenic diseases affecting Caucasians and has an incidence of approximately 1:3,300 births. Currently recommended screening panels for mutations in the responsible gene (CF transmembrane regulator gene, CFTR) do not detect all disease-associated mutations. Our laboratory offers extensive sequencing of the CFTR (ABCC7) gene (including the promoter, all exons and splice junction sites, and regions of selected introns) as a clinical test to detect mutations which are not found with conventional screening. The objective of this report is to summarize the findings of extensive CFTR sequencing from our first 157 consecutive patient samples. In most patients with classic CF symptoms (18/24, 75%), extensive CFTR sequencing confirmed the diagnosis by finding two disease-associated mutations. In contrast, only 5 of 75 (7%) patients with atypical CF had been identified with two CFTR mutations. A diagnosis of CF was confirmed in 10 of 17 (58%) newborns with either positive sweat chloride readings or positive immunoreactive trypsinogen (IRT) screen results. We ascertained ten novel sequence variants that are potentially disease-associated: two deletions (c.1641AG>T, c.2949_2853delTACTC), seven missense mutations (p.S158T, p.G451V, p.K481E, p.C491S, p.H949L, p.T1036N, p.F1099L), and one complex allele ([p.356_A357del; p.358I]). We ascertained three other apparently novel complex alleles. Finally, several patients were found to carry partial CFTR gene deletions. In summary, extensive CFTR gene sequencing can detect rare mutations which are not found with other screening and diagnostic tests, and can thus establish a definitive diagnosis in symptomatic patients with previously negative results. This enables carrier detection and prenatal diagnosis in additional family members.     

Iron and protein biofortification of cassava: lessons learned

Over two hundred and fifty million Africans rely on the starchy root crop cassava (Manihot esculenta) as their primary source of calories. Cassava roots, however, have the lowest protein:energy ratio of all the world's major staple crops. Furthermore, a typical cassava-based diet provides less than 10-20% of the required amounts of iron, zinc, vitamin A and vitamin E. The BioCassava Plus program employed modern biotechnologies to improve the health of Africans through development and delivery of novel cassava germplasm with increased nutrient levels. Here we describe the development of molecular strategies and their outcomes to meet minimum daily allowances for protein and iron in cassava based diets. We demonstrate that cyanogens play a central role in cassava nitrogen metabolism and that strategies employed to increase root protein levels result in reduced cyanogen levels in roots. We also demonstrate that enhancing root iron uptake has an impact on the expression of genes that regulate iron homeostasis in multiple tissues. These observations demonstrate the complex metabolic interactions involved in enhancing targeted nutrient levels in plants and identify potential new strategies for further enhancing nutrient levels in cassava.     

Negative-pressure wound therapy in the military: lessons learned

The utilization of negative pressure for medicinal purposes dates back to 600 bc. The U.S. military has been engaged in continuous overseas combat operations since 2001. Negative-pressure wound therapy has been in use in the treatment of casualties from these operations since 2004. It represents a new standard of practice in combat wound care; it promotes granulation tissue formation and creates mechanical forces supporting wound contraction, facilitating definitive wound closure. This article describes (1) the use of negative-pressure wound therapy in combat casualty care, (2) inherent challenges of its use in theater of operations and across the echelons of care, (3) modifications of this wound therapy to meet military-specific needs, and (4) future directions with this novel wound care modality.     

Amazonia and the modern carbon cycle: lessons learned

In this paper, we review some critical issues regarding carbon cycling in Amazonia, as revealed by several studies conducted in the Large Scale Biosphere Atmosphere Experiment in Amazonia (LBA). We evaluate both the contribution of this magnificent biome for the global net primary productivity/net ecosystem exchange (NPP/NEE) and the feedbacks of climate change on the dynamics of Amazonia. In order to place Amazonia in a global perspective and make the carbon flux obtained through the LBA project comparable with global carbon budgets, we extrapolated NPP/NEE values found by LBA studies to the entire area of the Brazilian Amazon covered by rainforest. The carbon emissions due to land use changes for the tropical regions of the world produced values from 0.96 to 2.4 Pg C year⁻¹, while atmospheric CO₂ inversion models have recently indicated that tropical lands in the Americas could be exchanging a net 0.62±1.15 Pg C year⁻¹ with the atmosphere. The difference calculated from these two methods would imply a local sink of approximately 1.6–1.7 Pg C year⁻¹, or a source of 0.85 ton C ha⁻¹ year⁻¹. Using our crude extrapolation of LBA values for the Amazon forests (5 million km²) we estimate a range for the C flux in the region of −3.0 to 0.75 Pg C year⁻¹. The exercise here does not account for environmental variability across the region, but it is an important driver for present and future studies linking local process (i.e. nutrient availability, photosynthetic capacity, and so forth) to global and regional dynamic approaches.     

Mitochondrial efficiency: lessons learned from transgenic mice

Metabolic research has, like most areas of research in the life sciences, been affected dramatically by the application of transgenic technologies. Within the specific area of bioenergetics it has been thought that transgenic approaches in mice would provide definitive proof for some longstanding metabolic theories and assumptions. Here we review a number of transgenic approaches that have been used in mice to address theories of mitochondrial efficiency. The focus is largely on genes that affect the coupling of energy substrate oxidation to ATP synthesis, and thus, mice in which the uncoupling protein (Ucp) genes are modified are discussed extensively. Transgenic approaches have indeed provided proof-of-concept in some instances, but in many other instances they have yielded results that are in contrast to initial hypotheses. Many studies have also shown that genetic background can affect phenotypic outcomes, and that the upregulated expression of genes that are related to the modified gene often complicates the interpretation of findings.     

Dissecting phosphorylation networks: lessons learned from yeast

Protein phosphorylation continues to be regarded as one of the most important post-translational modifications found in eukaryotes and has been implicated in key roles in the development of a number of human diseases. In order to elucidate roles for the 518 human kinases, phosphorylation has routinely been studied using the budding yeast Saccharomyces cerevisiae as a model system. In recent years, a number of technologies have emerged to globally map phosphorylation in yeast. In this article, we review these technologies and discuss how these phosphorylation mapping efforts have shed light on our understanding of kinase signaling pathways and eukaryotic proteomic networks in general.     

Introduction: microbiology and immunology: lessons learned from Salmonella.

Salmonella enterica, a Gram-negative bacterium, causes significant morbidity and mortality worldwide, and is an excellent model to study bacterial pathogenesis and cellular immune responses. With the development of powerful new technologies, there has been a fusion of research on immunology, molecular biology and cellular microbiology of S. enterica infections. This multidisciplinary research will enhance our understanding of the basic mechanisms of bacterial infections and immunity; it also provides new approaches towards therapeutic and control measures.     

Protein folding diseases and neurodegeneration: lessons learned from yeast

Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism for studying fundamental cellular processes across the eukaryotic kingdom including man. In this respect, complementation assays, in which the yeast protein is replaced by a homologous protein from another organism, have been very instructive. A newer trend is to use the yeast cell factory as a toolbox to understand cellular processes controlled by proteins for which the yeast lacks functional counterparts. An increasing number of studies have indicated that S. cerevisiae is a suitable model system to decipher molecular mechanisms involved in a variety of neurodegenerative disorders caused by aberrant protein folding. Here we review the current knowledge gained by the use of so-called humanized yeasts in the field of Huntington's, Parkinson's and Alzheimer's diseases.     

Tuberculin immunotherapy: its history and lessons to be learned

The use of tuberculin for the therapy of tuberculosis was attempted more than 100 years ago and abandoned because of its adverse reactions. In this historical review we point out that some of the intensive efforts to avoid the reactions were based on the best scientific rationale available at that time. Balancing the dosage and intervals of tuberculin delivery with clinical and laboratory monitoring of patients achieved a limited success, with implications, toward current research in the field. The role of economical and social aspects at that time is also a lesson to be learned toward current approaches to tuberculosis control.