How can the functional reponse best be determined?

Summary We evaluated three methods for the analysis of functional response data by asking whether a given method could discriminate among functional responses and whether it could accurately identify regions of positive density-dependent predation. We evaluated comparative curve fitting with foraging models, linear least-squares analysis using the angular transformation, and logit analysis. Using data from nature and simulations, we found that the analyses of predation rates with the angular transformation and logit analysis were best at consistently determining the true functional response, i.e. the model used to generate simulated data. These methods also produced the most accurate estimates of the true regions of density dependence. Of these two methods, functional response data best fulfill the assumptions of logit analysis. Angularly transformed predation rates only approximate the assumptions of linear leastsquares analysis for predation rates between 0.1 and 0.9. Lack-of-fit statistics can reveal inadequate fit of a model to a data set where simple regression statistics might erroneously suggest a good match.     

When can the cause of a population decline be determined?

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.     

Marine microbial diversity: can it be determined?

Estimates of the order of magnitude for the total number of microbial species on Earth range from 10(3) to 10(9). Despite global dispersal of microorganisms, this number is probably rather large. The total biodiversity of an ecosystem is composed of two elements: first, a set of abundant taxa that carry out most ecosystem functions, grow actively and suffer intense losses through predation and viral lysis. These taxa are retrievable with molecular techniques but are difficult to grow in culture. Second, there is a seed bank of many rare taxa that are not growing or grow extremely slowly, do not experience viral lysis and predation is reduced. Such taxa are seldom retrieved by molecular techniques but many can be grown in culture, which explains the dictum 'everything is everywhere'.     

How can good general practitioner care be achieved?

It has been shown that to provide a high standard of care general practitioners probably need to book consultations at intervals of at least 10 minutes. In this study the maximum list size for which a general practitioner might be expected to provide a high standard of care was determined from calculations of the time spent consulting, based on various consultation rates and list sizes and assuming that consultations were 10 minutes long. If good quality care is to be provided and is to include the range of services suggested in the government''s recent green paper average list sizes should probably be no more than 1750, and lower in areas of high demand and high need. In addition to this, minimum standards could be determined for such measures as facilities available in surgeries, practice records, and accessibility of doctors to ensure that basic services were offered by all general practitioners.     

How well can the accuracy of comparative protein structure models be predicted?

Comparative structure models are available for two orders of magnitude more protein sequences than are experimentally determined structures. These models, however, suffer from two limitations that experimentally determined structures do not: They frequently contain significant errors, and their accuracy cannot be readily assessed. We have addressed the latter limitation by developing a protocol optimized specifically for predicting the Calpha root-mean-squared deviation (RMSD) and native overlap (NO3.5A) errors of a model in the absence of its native structure. In contrast to most traditional assessment scores that merely predict one model is more accurate than others, this approach quantifies the error in an absolute sense, thus helping to determine whether or not the model is suitable for intended applications. The assessment relies on a model-specific scoring function constructed by a support vector machine. This regression optimizes the weights of up to nine features, including various sequence similarity measures and statistical potentials, extracted from a tailored training set of models unique to the model being assessed: If possible, we use similarly sized models with the same fold; otherwise, we use similarly sized models with the same secondary structure composition. This protocol predicts the RMSD and NO3.5A errors for a diverse set of 580,317 comparative models of 6174 sequences with correlation coefficients (r) of 0.84 and 0.86, respectively, to the actual errors. This scoring function achieves the best correlation compared to 13 other tested assessment criteria that achieved correlations ranging from 0.35 to 0.71.     

How can proteolipids be central players in membrane fusion?

Proton transport ATPases have been celebrated as rotating motors that energize membranes. Now studies of membrane fusion in yeast suggest that the hydrophobic subunits of the vacuolar ATPase participate in formation of fusion pores. This work confirms previous studies showing that membrane approximation by alpha-helical protein bundles is inadequate for complete intracellular fusion and reopens a debate over whether the core of the central intermediate of membrane fusion is lipidic or proteinaceous.     

How can genetically modified foods be made publicly acceptable?

A recent study by Lusk suggests that consumers might voluntarily pay more for a genetically modified (GM) food than a non-GM equivalent if made aware of the possible health benefits. However, other research indicates that the acceptability of novel hazards is affected by a variety of factors, in addition to benefits, and that making agricultural biotechnology publicly acceptable will be more complex than indicated by the results from Lusk's study.     

How can miscanthus fields be reintegrated into a crop rotation?

The bioeconomy, with its aim of replacing fossil by biobased resources, is increasingly focusing on biomass production from perennial crops, such as miscanthus. To date, research on miscanthus has explored a number of cultivation aspects; however, one major issue has not yet been addressed: How can former miscanthus fields be reintegrated into a crop rotation? This encompasses the questions of which following crop most efficiently suppresses resprouting miscanthus and what happens to the soil nitrogen content after a miscanthus removal. This study aimed to answer both questions. For this purpose, four spring crops (ryegrass, rapeseed, barley, maize) and fallow as control were cultivated after a Miscanthus sinensis removal. To test the effect of the removal on soil nitrogen content, each spring crop (excluding fallow) was divided into fertilized and unfertilized plots. After the spring crop harvest, winter wheat was cultivated to clarify which spring crop had most efficiently suppressed the resprouting miscanthus. The results indicate that fertilized crops had 35% less miscanthus biomass per hectare than unfertilized crops, probably due to the higher plant density and/or better development of the fertilized crops during the growing season. The soil mineral nitrogen (N_min) content was found to increase during the vegetation period following the miscanthus removal (average +14.85 kg/ha), but was generally on a low level. We conclude that nitrogen from miscanthus residues is partly fixed in organic matter and is thus not plant‐available in the first cropping season. As some nitrogen is supplied by the decomposition of miscanthus residues, our results suggest that the crop cultivated after a miscanthus removal requires less fertilization. Of all the follow‐on spring crops tested, maize coped with the prevailing soil conditions and resprouting miscanthus most efficiently, resulting in satisfactory yields, and thus seems to be a suitable crop for cultivation after miscanthus.     

Ligand binding strategies of human serum albumin: How can the cargo be utilized?

Human serum albumin (HSA), being the most abundant carrier protein in blood and a modern day clinical tool for drug delivery, attracts high attention among biologists. Hence, its unfolding/refolding strategies and exogenous/endogenous ligand binding preference are of immense use in therapeutics and clinical biochemistry. Among its fellow proteins albumin is known to carry almost every small molecule. Thus, it is a potential contender for being a molecular cargo/or nanovehicle for clinical, biophysical and industrial purposes. Nonetheless, its structure and function are largely regulated by various chemical and physical factors to accommodate HSA to its functional purpose. This multifunctional protein also possesses enzymatic properties which may be used to convert prodrugs to active therapeutics. This review aims to highlight current overview on the binding strategies of protein to various ligands that may be expected to lead to significant clinical applications. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

How can elongation factors EF-G and EF-Tu discriminate the functional state of the ribosome using the same binding site?

Elongation factors EF-G and EF-Tu are structural homologues and share near-identical binding sites on the ribosome, which encompass the GTPase-associated centre (GAC) and the sarcin-ricin loop (SRL). The SRL is fixed structure in the ribosome and contacts elongation factors in the vicinity of their GTP-binding site. In contrast, the GAC is mobile and we hypothesize that it interacts with the alpha helix D of the EF-Tu G-domain in the same way as with the alpha helix A of the G'-domain of EF-G. The mutual locations of these helices and GTP-binding sites in the structures of EF-Tu and EF-G are different. Thus, the orientation of the GAC relative to the SRL determines whether EF-G or EF-Tu will bind to the ribosome.     

Cancer therapy: can the challenge be MET?

The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors and is often associated with the acquisition of an aggressive phenotype. The Met oncogene, encoding the RTK for hepatocyte growth factor (HGF), controls genetic programs leading to cell growth, invasion and protection from apoptosis. The deregulated activation of Met is crucial not only for the acquisition of tumorigenic properties but also to achieve an invasive phenotype. The involvement of MET in human tumors has been definitively established and can be achieved through several mechanisms, including MET interaction with unrelated membrane receptors, such as integrins, plexins, CD44, FAS and other RTKs. Interfering with Met activation is thus a new and challenging approach to hamper tumorigenic and metastatic processes.