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Plant genetics: out with the old, in with the new?

Plant breeding represents an evolving technology based largely on genetic principles. Approximately one-half of the increased yields of major crop plants can be attributed to the genetic improvement of the crop. Although the breeding technology and undergirding science are sound, additional information on the biochemical pathways underlying agronomic and quality traits and their genetic control would allow new genetic technologies to be used more fully. Current developments in molecular biology, plant cell and tissue culture, genetic engineering, and use of molecular genetics will facilitate the selection of complex traits. Genetic improvement of plants in the future will be based on an integration of modern plant-breeding methods and the new genetic technologies. Thus, the new genetic approaches do not represent a replacement technology but will add to the arsenal of tools available for improving crops.

Agriculture↗

The cell membrane and cell signals: new targets for novel anticancer drugs.

In the concluding Discussion session, emphasis focussed on the potential for interfering selectively with cell membranes and cell signalling in tumour as against normal tissues. There could be no doubt that tremendous advances are being made in our understanding of the molecular changes associated with malignancy and that the information available for the rational design of inhibitors of particular signalling pathways is increasingly sophisticated. There was a consensus that we need more information on the qualitative and quantitative differences in the structure and function of membranes and the signalling machinery in various normal tissues as compared to their cancerous counterparts. Ideally we will develop drug against, for example, specific forms of, let us say, protein kinase C or tyrosine kinase which are found to be predominantly active in neoplastic cells. This may well prove possible, at least in some instances, in which case a safe therapeutic margin will be assured. But differences may in other situations turn out to be in the level of expression rather than purely qualitative in nature, and the scale of the disparate expression may not always be great. Even in such situations, adequate therapeutic selectivity may still be achieved. This may derive from a "damping down" of signalling in the hyperactive tumour. Although there are legitimate concerns regarding the possible toxic effects of administering signal-wrecking molecules in man, we should not be pessimistic as there are clear precedents elsewhere in medicine for drugs acting on membrane signals proving to be safe and effective against expectation informed by hindsight. There may also be concerns about new forms of drug resistance. But this will be so for any new agent or novel target. And with mechanism of action clearly to the fore we should be able to predict resistance pathways in advance and devise appropriate circumvention strategies or targeted second line therapies. There was a palpable buzz at the meeting that this is a valid, different and above all rational approach. Not only that, but the new therapeutic molecules which we discover will themselves prove to be valuable tools with which to probe further into the mechanisms of malignancy and signal transduction. We had expected to see a bewildering amount of new information from the basic sciences of molecularbiology and cell physiology, and we got it. But it was also impressive to witness the number of new compounds coming through which look like real drugs or at least exciting lead compounds. The membrane-active ether lipids are in clinical trial. Bryostatin 1 will shortly join them.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Molecular anatomy and molecular design of channel proteins.

A central goal in membrane biology is to understand how channel proteins work in terms of their underlying protein structures. Ionic channels are symmetric (or pseudosymmetric) transmembrane protein assemblies organized around a central aqueous pore. The two key functional elements are the ionic channel, the actual polar pathway that permits the selective passage of 10(8) ions per second across the apolar core of the membrane lipid bilayer, and the sensor, the structure that detects the stimulus and couples it to the opening or closing (gating) of the channel. The current excitement in membrane protein science emerges from structural information that is providing clues about the molecular determinants of function: molecular cloning and sequencing has led to the elucidation of the primary structures of several superfamilies of voltage-gated and ligand-gated channels; channel proteins have been purified and reconstituted in lipid bilayers with full retention of function; the properties of many channel proteins have been characterized at the single-channel level; cDNA or RNA transcripts have been expressed in oocytes as functional proteins; specific peptide sequences predicted by molecular modeling to form the channel lining have been synthesized by solid-phase methods and proved to be channel formers in lipid bilayers. These advances are beginning to delineate general principles about the molecular design of this class of proteins that are essential for cellular excitability and signal transduction.

Amino Acid Sequence↗

The Human Genome Project: an update.

The mapping, sequencing, and analysis of the human genome that has occurred during the last decade through the Human Genome Project are providing fundamental advances for basic science and medicine. Genomic information is providing insights into causes of, susceptibility to, and protection from cancer and a host of other diseases. Already, information generated by the Human Genome Project has been incorporated into the care of cancer patients. Perhaps more so than other types of medical information, genetic knowledge can have profound implications for individuals, families, and society. As a result, nursing professionals in clinical and academic settings are being called upon to identify and deliberate medical, social, ethical, and legal issues stemming from Human Genome Project advancements. The purpose of this article is to review the goals and implications of the Human Genome Project to further prepare cancer nurses to actively participate in the deliberations, research, and clinical activities evolving from the Human Genome Project.

Genome, Human↗

Family physician continuity of care and emergency department use in end-of-life cancer care.

BACKGROUND: Despite cancer patients preferring to spend their last days out-of-hospital, many make difficult visits to the emergency department (ED). Family physician continuity of care has been shown in some clinical situations to reduce ED utilization. OBJECTIVE: To determine if greater family physician continuity of care for cancer patients during the end-of-life is associated with less ED utilization. METHOD: This retrospective, population-based study involved secondary analysis of linked administrative data files for 1992 to 1997. Sources included the Nova Scotia Cancer Registry, Vital Statistics, the Queen Elizabeth II Health Sciences Center Oncology Patient Information System and Palliative Care Program (PCP), Hospital Admissions/Separation data, and Physician Services information. Subjects included adults with a recorded date of cancer diagnosis who died of cancer and who had made at least three visits to a family physician during their last 6 months of life. The relationship between total ED visits and family physician continuity of care, developed using the Modified Modified Continuity Index (MMCI), was examined using negative binomial regression with adjustments for survival, year of death, sex, age, cancer type, region, PCP admission, specialty visits, hospital days, death location, income quintile, and total ambulatory visits. RESULTS: In total, 8702 subjects made 11,551 ED visits (median = 1.0); median MMCI was 0.83. Adjusted results indicate those experiencing low continuity (MMCI < 0.5) made 3.9 times more ED visits (rate ratio [RR] = 3.93; 95% CI [CI] = 3.57-4.34) than those experiencing high continuity (MMCI > or = 0.8) and patients experiencing moderate continuity (MMCI = 0.5-0.8) made twice as many ED visits (RR = 2.28; CI = 2.15-2.42). CONCLUSION: Given this significant association between family physician continuity of care and ED visits during the end-of-life, and given international trends to reform primary care, active planning of strategies to facilitate such continuity should be encouraged.

Aged↗

Consumer-phase Salmonella enterica serovar enteritidis risk assessment for egg-containing food products.

We describe a one-dimensional probabilistic model of the role of domestic food handling behaviors on salmonellosis risk associated with the consumption of eggs and egg-containing foods. Six categories of egg-containing foods were defined based on the amount of egg contained in the food, whether eggs are pooled, and the degree of cooking practiced by consumers. We used bootstrap simulation to quantify uncertainty in risk estimates due to sampling error, and sensitivity analysis to identify key sources of variability and uncertainty in the model. Because of typical model characteristics such as nonlinearity, interaction between inputs, thresholds, and saturation points, Sobol's method, a novel sensitivity analysis approach, was used to identify key sources of variability. Based on the mean probability of illness, examples of foods from the food categories ranked from most to least risk of illness were: (1) home-made salad dressings/ice cream; (2) fried eggs/boiled eggs; (3) omelettes; and (4) baked foods/breads. For food categories that may include uncooked eggs (e.g., home-made salad dressings/ice cream), consumer handling conditions such as storage time and temperature after food preparation were the key sources of variability. In contrast, for food categories associated with undercooked eggs (e.g., fried/soft-boiled eggs), the initial level of Salmonella contamination and the log10 reduction due to cooking were the key sources of variability. Important sources of uncertainty varied with both the risk percentile and the food category under consideration. This work adds to previous risk assessments focused on egg production and storage practices, and provides a science-based approach to inform consumer risk communications regarding safe egg handling practices.

Bacteriophage Typing↗

Hydrogeological research: beginning of the end or end of the beginning?

This paper uses citation data to assess whether articles published in key ground water journals such as Ground Water (GW) and Water Resources Research (WRR) are impacting research. Citation information was obtained from SCI Journal Citation Reports and The Web of Science--databases maintained by the Institute for Scientific Information (ISI). Information extracted from The Web of Science was processed further to remove corrections to papers, discussion/replies, and book reviews. Generally, there are many ground water papers published, but citations of these papers are limited. Approximately 10% to 15% of WRR articles, and 2% to 3% of GW articles attract more than 50 citations in their lifetimes. In both GW and WRR, the top 10% of papers eventually will contribute nearly half of the total yearly citations. Another emerging trend is a diminishing emphasis on citations to new work as compared to work more than 10 years in age. When articles in Ground Water or Journal of Hydrology cite papers in Water Resources Research, those papers cite work 10 or more years old half of the time. If one believes that citations are a measure of science impact, then there is cause for concern. Research is inefficient with much produced for little gain. On a typical industrial life-cycle curve, ground water research is likely ranked as mature and close to aging. At this stage, much work will have been completed and the number of truly impactful problems will have dwindled to just a few.

Diffusion of Innovation↗

Multidisciplinary collaboration in fieldwork: Australian studies.

The Australian situation offers special insights for cross-cultural psychiatric research. The two cultures that "crossed" in Australia were diametrically opposed in their characteristics. Suffering, which is considered to be the raison d'être of cross-cultural psychiatry, became pandemic among Aborigines, not only because the invading society was ruthlessly aggressive, but also because the invaded society did not have the social institutions and modal personality patterns enabling it to adapt to the introduced culture. It is suggested that no applied science makes more demands of more scientific disciplines than does cross-cultural psychiatry. Psychiatry itself is a multidisciplinary science. The amount of information needed by the cross-cultural extension of psychiatry is further expanded. Only a multidisciplinary approach can furnish the necessary level of information. An outline is given of multidisciplinary field work in Australia, indicating advantages and difficulties inherent in it. Attention is drawn to literature in which details of the results may be found. The Australian work leads to the conclusion that if the relief of suffering is the aim then greater involvement is needed in cross-cultural psychiatry from the culture that has been "crossed".

Australia↗

Binary bacterial toxins: biochemistry, biology, and applications of common Clostridium and Bacillus proteins.

Certain pathogenic species of Bacillus and Clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic "A-B" paradigm for protein toxins. The binary toxins produced by B. anthracis, B. cereus, C. botulinum, C. difficile, C. perfringens, and C. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. The "B" components are synthesized as precursors that are subsequently activated by serine-type proteases on the targeted cell surface and/or in solution. Following release of a 20-kDa N-terminal peptide, the activated "B" components form homoheptameric rings that subsequently dock with an "A" component(s) on the cell surface. By following an acidified endosomal route and translocation into the cytosol, "A" molecules disable a cell (and host organism) via disruption of the actin cytoskeleton, increasing intracellular levels of cyclic AMP, or inactivation of signaling pathways linked to mitogen-activated protein kinase kinases. Recently, B. anthracis has gleaned much notoriety as a biowarfare/bioterrorism agent, and of primary interest has been the edema and lethal toxins, their role in anthrax, as well as the development of efficacious vaccines and therapeutics targeting these virulence factors and ultimately B. anthracis. This review comprehensively surveys the literature and discusses the similarities, as well as distinct differences, between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine. The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria.

Animals↗

Patient satisfaction and normative decision theory.

This article explores the application of normative decision theory (NDT) to the challenge of facilitating and measuring patient satisfaction. Patient satisfaction is the appraisal, by an individual, of the extent to which the care provided has met that individual's expectations and preferences. Classic decision analysis provides a graphic and computational strategy to link patient preferences for outcomes to the treatment choices likely to produce the outcomes. Multiple criteria models enable the complex judgment task of measuring patient satisfaction to be decomposed into elemental factors that reflect patient preferences, thus facilitating evaluation of care in terms of factors relevant to the individual patient. Through the application of NDT models, it is possible to use patient preferences as a guide to the treatment planning and care monitoring process and to construct measures of patient satisfaction that are meaningful to the individual. Nursing informatics, with its foundations in both information management and decision sciences, provides the tools and data necessary to promote care provided in accord with patient preferences and to ensure appraisal of satisfaction that aptly captures the complex, multidimensional nature of patient preferences.

Decision Theory↗

The role of a scientific society in physiology education: current and future perspectives.

As a professional society of physiologists involved in research and teaching, the American Physiological Society (APS) is "...devoted to fostering education, scientific research, and the dissemination of information in the physiological sciences." Established long-range goals for education guide the development of current and future programs at all education levels. K-12 outreach programs develop working relationships between physiologists and K-12 teachers within local communities and improve the quality of precollege science education. At the undergraduate level, APS programs foster excellence in physiology education and promote student interest in physiology careers. At the graduate level, activities promote excellence in graduate training and the professional development of students, including a focus on underrepresented groups. At each of these levels, the Society includes activities for the continuing education of its members. Looking to the future, the Society plans to expand the programs and resources offered to researchers and educators at all levels. On-line programs, resources, and communications have been initiated and will play an even more important role in the future.

Adult↗