Who should benefit financially from a good idea?

The need to publish ideas so that they can be explored, debated and extended by others before they are fully tested in the lab or the clinic is in conflict with the need to patent those ideas to provide a commercial incentive to apply them. I discuss why this conflict occurs, why it is important, and suggest three ways to get round it: root-and-branch reform of patent law (which seems impossible), extension of the US system's ‘grace period’ between publishing and filing a patent to longer times in the US and implementing the same system in other countries (which seems unlikely to happen), and binding readers of journals with a network of optional confidentiality agreements that allow publication but not citation without the authors’ permission. This latter appears too complex and conflicting an idea to work either, but while many conflicts with common scientific practice exist, the complexity of the system need not deter us, as at root the idea is simple and so it could be managed by software instead of patent lawyers.     

Is it a revolution?

Jablonka and Lamb's claim that evolutionary biology is undergoing a ‘revolution’ is queried. But the very concept of revolutionary change has uncertain application to a field organized in the manner of contemporary biology. The explanatory primacy of sequence properties is also discussed.

Is infertility a disease and does it matter?

Claims about whether or not infertility is a disease are sometimes invoked to defend or criticize the provision of state‐funded treatment for infertility. In this paper, I suggest that this strategy is problematic. By exploring infertility through key approaches to disease in the philosophy of medicine, I show that there are deep theoretical disagreements regarding what subtypes of infertility qualify as diseases. Given that infertility’s disease status remains unclear, one cannot uncontroversially justify or undermine its claim to medical treatment by claiming that it is or is not a disease. Instead of focusing on disease status, a preferable strategy to approach the debate about state‐funded treatment is to explicitly address the specific ethical considerations raised by infertility. I show how this alternative strategy can be supported by a recent theoretical framework in the philosophy of medicine which avoids the problems associated with the concepts of health and disease.     

Is canalization more than just a beautiful idea?

The heat-shock protein 90 (Hsp90) is currently thought to buffer eukaryotic cells against perturbations caused by pre-existing cryptic genetic variation. A new study suggests that the buffering function of Hsp90 could instead be due to its repression of de novo transposon-mediated mutagenesis.     

Connectance of species interaction networks and conservation value: Is it any good to be well connected?

Recently, the focus of conservation efforts gradually changed from a species-centred approach to a broader ambition of conserving functional ecosystems. This new approach relies on the understanding that much ecosystem function is a result of the interaction of species to form complex interaction networks. Therefore measures summarising holistic attributes of such ecological networks have the potential to provide useful indicators to guide and assess conservation objectives. The most generally accepted insight is that complexity in species interactions, measured by network connectance, is an important attribute of healthy communities which usually protects them from secondary extinctions. An implicit and overlooked corollary to this generalization is that conservation efforts should be directed to conserve highly connected communities. We conducted a literature review to search for empirical evidence of a relationship between connectance (complexity) and conservation value (communities on different stages of degradation). Our results show that the often assumed positive relationship between highly connected and desirable (i.e. with high conservation value) communities does not derive from empirical data and that the topic deserves further discussion. Given the conflicting empirical evidence revealed in this study, it is clear that connectance on its own cannot provide clear information about conservation value. In the face of the ongoing biodiversity crisis, studies of species interaction networks should incorporate the different ‘conservation value’ of nodes (i.e. species) in a network if it is to be of practical use in guiding and evaluating conservation practice.     

Is it going to be SIN?

Insertional mutagenesis resulting in a leukaemia-like lymphoproliferative disease, as observed in the X-SCID (severe combined immunodeficiency) clinical trial using a gamma-retroviral vector that transferred a functional copy of the defective gene into hematopoietic precursor cells of affected children, sparked a debate about a ban on conventional gamma-retroviral vectors. This commentary summarizes the relevant data on this topic and concludes that there is no preclinical or clinical evidence as yet that SIN vectors, which self-inactivate the retroviral long terminal repeats (LTRs), will indeed show an improved safety profile. Conventional murine leukaemia virus (MLV) vectors can thus be used further in clinical gene therapy trials but require a thorough case-by-case risk-benefit analysis.     

Is it better to combine predictions?

We have compared the accuracy of the individual protein secondary structure prediction methods: PHD, DSC, NNSSP and Predator against the accuracy obtained by combing the predictions of the methods. A range of ways of combing predictions were tested: voting, biased voting, linear discrimination, neural networks and decision trees. The combined methods that involve 'learning' (the non-voting methods) were trained using a set of 496 non-homologous domains; this dataset was biased as some of the secondary structure prediction methods had used them for training. We used two independent test sets to compare predictions: the first consisted of 17 non-homologous domains from CASP3 (Third Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction); the second set consisted of 405 domains that were selected in the same way as the training set, and were non-homologous to each other and the training set. On both test datasets the most accurate individual method was NNSSP, then PHD, DSC and the least accurate was Predator; however, it was not possible to conclusively show a significant difference between the individual methods. Comparing the accuracy of the single methods with that obtained by combing predictions it was found that it was better to use a combination of predictions. On both test datasets it was possible to obtain a approximately 3% improvement in accuracy by combing predictions. In most cases the combined methods were statistically significantly better (at P = 0.05 on the CASP3 test set, and P = 0.01 on the EBI test set). On the CASP3 test dataset there was no significant difference in accuracy between any of the combined method of prediction: on the EBI test dataset, linear discrimination and neural networks significantly outperformed voting techniques. We conclude that it is better to combine predictions.     

Is it really good for you to eat fat as much as you could?

正High carbohydrate(CHO)intake was associated with higher risk of total mortality,whereas high intake of total fat and individual types of fat were related to lower total mortality.Total fat and types of fat were not associated with cardiovascular disease,myocardial infarction,or cardiovascu-     

Is it better to add taxa or characters to a difficult phylogenetic problem?

The effects on phylogenetic accuracy of adding characters and/or taxa were explored using data generated by computer simulation. The conditions of this study were constrained but allowed for systematic investigation of certain parameters. The starting point for the study was a four-taxon tree in the "Felsenstein zone," representing a difficult phylogenetic problem with an extreme situation of long branch attraction. Taxa were added sequentially to this tree in a manner specifically designed to break up the long branches, and for each tree data matrices of different sizes were simulated. Phylogenetic trees were reconstructed from these data using the criteria of parsimony and maximum likelihood. Phylogenetic accuracy was measured in three ways: (1) proportion of trees that are completely correct, (2) proportion of correctly reconstructed branches in all trees, and (3) proportion of trees in which the original four-taxon statement is correctly reconstructed. Accuracy improved dramatically with the addition of taxa and much more slowly with the addition of characters. If taxa can be added to break up long branches, it is much more preferable to add taxa than characters.     

Is it a paradox or misinterpretation?

The paradox recently raised by Wang and Yuan (Proteins 2000;38:165-175) in protein structural class prediction is actually a misinterpretation of the data reported in the literature. The Bayes decision rule, which was deemed by Wang and Yuan to be the most powerful method for predicting protein structural classes based on the amino acid composition, and applied by these investigators to derive the upper limit of prediction rate for structural classes, is actually completely the same as the component-coupled algorithm proposed by previous investigators (Chou et al., Proteins 1998;31:97-103). Owing to lack of a complete or near-complete training data set, the upper limit rate thus derived by these investigators might be both invalid and misleading. Clarification of these points will further stimulate investigation of this interesting area.     

Is it possible to produce succinic acid at a low pH?

Bio-based succinate is still a matter of special emphasis in biotechnology and adjacent research areas. The vast majority of natural and engineered producers are bacterial strains that accumulate succinate under anaerobic conditions. Recently, we succeeded in obtaining an aerobic yeast strain capable of producing succinic acid at low pH. Herein, we discuss some difficulties and advantages of microbial pathways producing "succinic acid" rather than "succinate." It was concluded that the peculiar properties of the constructed yeast strain could be clarified in view of a distorted energy balance. There is evidence that in an acidic environment, the majority of the cellular energy available as ATP will be spent for proton and anion efflux. The decreased ATP:ADP ratio could essentially reduce the growth rate or even completely inhibit growth. In the same way, the preference of this elaborated strain for certain carbon sources could be explained in terms of energy balance. Nevertheless, the opportunity to exclude alkali and mineral acid waste from microbial succinate production seems environmentally friendly and cost-effective.