What are the organismic elements of vegetation science?

The recent inclusion of communities of planktonic algae and microbial crusts into the system of European vegetation types is critically discussed. It is argued that formal vegetation classification should be limited to plant taxa represented by macroscopic individuals within a plot, including all vascular plants, bryophytes, lichens, charophyta and macrophytic chlorophyta, rhodophyta or phaeophyta. In the interest of comparability and methodological stringency, all microscopic algae and all prokaryotes, including cyanobacteria, and the habitats dominated by such microorganisms (e.g. plankton, biofilms and crusts), should be excluded from vegetation classification.     

Can science justify regulatory decisions about the cultivation of transgenic crops?

Results of scientific studies are sometimes claimed to provide scientific justification for regulatory decisions about the cultivation of certain transgenic crops. A decision may be scientifically justified if objective analysis shows that the decision is more likely than alternatives to lead to the achievement of specific policy objectives. If policy objectives are not defined operationally, as is often the case, scientific justification for decisions is not possible. The search for scientific justification for decisions leads to concentration on reducing scientific uncertainty about the behaviour of transgenic crops instead of reducing uncertainty about the objectives of policies that regulate their use. Focusing on reducing scientific uncertainty at the expense of clarifying policy objectives may have detrimental effects on scientists, science and society.     

What do we know about the mechanisms of aromatase inhibitor resistance?

Clinical trials have demonstrated the importance of aromatase inhibitor (AI) therapy in the effective treatment of hormone-dependent breast cancers. Yet, as with all prolonged drug therapy, resistance to aromatase inhibitors does develop. To date, the precise mechanism responsible for resistance to aromatase inhibitors is not completely understood. In this paper, several mechanisms of de novo/intrinsic resistance and acquired resistance to AIs are discussed. These mechanisms are hypothesized based on important findings from a number of laboratories.

To better understand this question, our lab has generated, in vitro, breast cancer cell lines that are resistant to aromatase inhibitors. Resistant cell lines were generated over a prolonged period of time using the MCF-7aro (aromatase overexpressed) breast cancer line. These cell lines are resistant to the aromatase inhibitors letrozole, anastrozole and exemestane and the anti-estrogen tamoxifen, for comparison. Two types of resistant cell lines have been generated, those that grow in the presence of testosterone (T) which is needed for cell growth, and resistant lines that are cultured in the presence of inhibitor only (no T). In addition to functional characterization of aromatase and ER in these resistant cell lines, microarray analysis has been employed in order to determine differential gene expression within the aromatase inhibitor resistant cell lines versus tamoxifen, in order to better understand the mechanism responsible for AI resistance on a genome-wide scale. We anticipate that our studies will generate important information on the mechanisms of AI resistance. Such information can be valuable for the development of treatment strategies against AI-resistant breast cancers.     

What is the subject of science "bioinformatics"?

The paper is concerned with some problems of terminology, in particular the term "bioinformatics". In the last few years, the term "bioinformatics" has been intensively used among molecular biologists to indicate a subject that is only a constituent of genomics and is considered to involve a computer-assisted analysis of all data on nucleotide sequences of DNA. However, a wide circle of scientists, including biologists, physicists, mathematicians, and specialists in the field of cybernetics, informatics, and other disciplines have accepted and accept, as a rule, the "bioinformatics" as a synonym of science cybernetics and as a successor of this science. In this case, the subject of science "bioinformatics" should embrace not only genomics but practically all sections of the biological science. It should involve a study of information processes (storage, transfer, and processing of information, etc.) participating in the regulation and control at all levels of living systems, from macromolecules to the brain of higher animals and human.     

Animal morality: What is the debate about?

Empirical studies of the social lives of non-human primates, cetaceans, and other social animals have prompted scientists and philosophers to debate the question of whether morality and moral cognition exists in non-human animals. Some researchers have argued that morality does exist in several animal species, others that these species may possess various evolutionary building blocks or precursors to morality, but not quite the genuine article, while some have argued that nothing remotely resembling morality can be found in any non-human species. However, these different positions on animal morality generally appear to be motivated more by different conceptions of how the term “morality” is to be defined than by empirical disagreements about animal social behaviour and psychology. After delving deeper into the goals and methodologies of various of the protagonists, I argue that, despite appearances, there are actually two importantly distinct debates over animal morality going on, corresponding to two quite different ways of thinking about what it is to define “morality”, “moral cognition”, and associated notions. Several apparent skirmishes in the literature are thus cases of researchers simply talking past each other. I then focus on what I take to be the core debate over animal morality, which is concerned with understanding the nature and phylogenetic distribution of morality conceived as a psychological natural kind. I argue that this debate is in fact largely terminological and non-substantive. Finally, I reflect on how this core debate might best be re-framed.     

What can the structures of enzyme-inhibitor complexes tell us about the structures of enzyme substrate complexes?

Proteinases perform many beneficial functions that are essential to life, but they are also dangerous and must be controlled. Here we focus on one of the control mechanisms: the ubiquitous presence of protein proteinase inhibitors. We deal only with a subset of these: the standard mechanism, canonical protein inhibitors of serine proteinases. Each of the inhibitory domains of such inhibitors has one reactive site peptide bond, which serves all the cognate enzymes as a substrate. The reactive site peptide bond is in a combining loop which has an identical conformation in all inhibitors and in all enzyme-inhibitor complexes. There are at least 18 families of such inhibitors. They all share the conformation of the combining loops but each has its own global three-dimensional structure. Many three-dimensional structures of enzyme-inhibitor complexes were determined. They are frequently used to predict the conformation of substrates in very short-lived enzyme-substrate transition state complexes. Turkey ovomucoid third domain and eglin c have a Leu residue at P(1). In complexes with chymotrypsin, these P(1) Leu residues assume the same conformation. The relative free energies of binding of P(1) Leu (relative to either P(1) Gly or P(1) Ala) are within experimental error, the same for complexes of turkey ovomucoid third domain, eglin c, P(1) Leu variant of bovine pancreatic trypsin inhibitor and of a substrate with chymotrypsin. Therefore, the P(1) Leu conformation in transition state complexes is predictable. In contrast, the conformation of P(1) Lys(+) is strikingly different in the complexes of Lys(18) turkey ovomucoid third domain and of bovine pancreatic trypsin inhibitor with chymotrypsin. The relative free energies of binding are also quite different. Yet, the relative free energies of binding are nearly identical for Lys(+) in turkey ovomucoid third domain and in a substrate, thus allowing us to know the structure of the latter. Similar reasoning is applied to a few other systems.     

What do we know about the secretion and degradation of incretin hormones?

The incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine cells located in the intestinal mucosa, and act to enhance meal-induced insulin secretion. GIP and GLP-1 concentrations in the plasma rise rapidly after food ingestion, and the presence of unabsorbed nutrients in the intestinal lumen is a strong stimulus for their secretion. Nutrients can stimulate release of both hormones by direct contact with the K-cell (GIP) and L-cell (GLP-1), and this may be the most important signal. However, nutrients also stimulate GLP-1 and GIP secretion indirectly via other mechanisms. Incretin hormone secretion can be modulated neurally, with cholinergic muscarinic, beta-adrenergic and peptidergic (gastrin-releasing peptide, GRP) fibres generally having positive effects, while secretion is restrained by alpha-adrenergic and somatostatinergic fibres. Hormonal factors may also influence incretin hormone secretion. Somatostatin exerts a local inhibitory effect on the activity of both K- and L-cells via a paracrine mechanism, while, in rodents at least, GIP from the proximal intestine has a stimulatory effect on GLP-1 secretion, possibly mediated via a neural loop involving GRP. Once they have been released, both GLP-1 and GIP are subject to rapid degradation. The ubiquitous enzyme, dipeptidyl peptidase IV (DPP IV) cleaves N-terminally, removing a dipeptide and thereby inactivating both peptides, because the N-terminus is crucial for receptor binding. Subsequently, the peptides may be degraded by other enzymes and extracted in an organ-specific manner. The intact peptides are inactivated during passage across the hepatic bed and further metabolised by the peripheral tissues, while the kidney is important for the final elimination of the metabolites.     

What Can the Kinetics of Amyloid Fibril Formation Tell about Off-pathway Aggregation?

Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.     

What to do about fraud charges in science; or, will the Burt affair ever end?

Shortly after the death, in 1971, of Cyril Burt, a prominent British psychologist, the authenticity of his accounts of intelligence test results from the largest reported sample of MZA's (monozygotic twins reared apart) was challenged. Charges of fraud by Burt's critics and countercharges by his supporters started an acrimonious battle of words in journals, books, and the mass media that seesawed over the decades. It is still not resolved. The problematic ways in which the scientific community and its major organizations and journal editors have dealt or failed to deal with the problem are discussed. This revised version was published online in August 2006 with corrections to the Cover Date.     

What do Wessex general practitioners think about the structure of hospital vocational training?

OBJECTIVES--To assess the views of general practitioners about the structure and content of hospital vocational training and its relation to the training year. DESIGN--Postal questionnaire. SETTING--Wessex, England. SUBJECTS--General practitioner trainees undertaking practice training year (n = 144), course organisers (n = 22), and a random sample of two thirds of trainers (n = 135). RESULTS--Questionnaires were returned from 86% (260): 84% of trainees (121), 92% of trainers (124), and 68% of course organisers (15). Most respondents in all groups (84.3%, 95% confidence interval 79.7% to 88.8%) wanted more jobs lasting two and three months to allow a greater range of hospital specialties to be experienced and some of the training year to be carried out before hospital jobs (66.3%, 60.4% to 72.1%). Most hospital specialties were rated at least 6 out of 10 as "useful" for general practice training. A substantial minority of training posts did not have regular weekly teaching (166/541; 30.7%, 26.8% to 34.6%) and had no half day (224/541; 41.4%, 37.3% to 45.6%), and over half gave no study leave (293/541; 54.2%, 50.0% to 58.4%). CONCLUSIONS--The structure of hospital training should be reviewed as it does not reflect the views of most trainees, course organisers, or trainers. Individual posts need closer supervision to ensure the availability of basic training requirements. More trainees should be allowed to spend a short time in the general practice before hospital rotations and to choose a greater range of shorter jobs.