Articular cartilage collagen: an irreplaceable framework?

Adult articular cartilage by dry weight is two-thirds collagen. The collagen has a unique molecular phenotype. The nascent type II collagen fibril is a heteropolymer, with collagen IX molecules covalently linked to the surface and collagen XI forming the filamentous template of the fibril as a whole. The functions of collagens IX and XI in the heteropolymer are far from clear but, evidently, they are critically important since mutations in COLIX and COLXI genes can result in chondrodysplasia syndromes. Here we review what is known of the collagen assembly and present new evidence that collagen type III becomes covalently added to the polymeric fabric of adult human articular cartilage, perhaps as part of a matrix repair or remodelling process

A non-linear optimal estimation inverse method for radio occultation measurements of temperature, humidity and surface pressure

An optimal estimation inverse method is presented which can be used to retrieve simultaneously vertical profiles of temperature and specific humidity, in addition to surface pressure, from satellite-to-satellite radio occultation observations of the Earth's atmosphere. The method is a non-linear, maximum {\it a posteriori} technique which can accommodate most aspects of the real radio occultation problem and is found to be stable and to converge rapidly in most cases. The optimal estimation inverse method has two distinct advantages over the analytic inverse method in that it accounts for some of the effects of horizontal gradients and is able to retrieve optimally temperature and humidity simultaneously from the observations. It is also able to account for observation noise and other sources of error. Combined, these advantages ensure a realistic retrieval of atmospheric quantities. A complete error analysis emerges naturally from the optimal estimation theory, allowing a full characterisation of the solution. Using this analysis a quality control scheme is implemented which allows anomalous retrieval conditions to be recognised and removed, thus preventing gross retrieval errors. The inverse method presented in this paper has been implemented for bending angle measurements derived from GPS/MET radio occultation observations of the Earth. Preliminary results from simulated data suggest that these observations have the potential to improve NWP model analyses significantly throughout their vertical range.Comment: 18 (jgr journal) pages, 7 figure

Fluctuating selection models and Mcdonald-Kreitman type analyses

It is likely that the strength of selection acting upon a mutation varies through time due to changes in the environment. However, most population genetic theory assumes that the strength of selection remains constant. Here we investigate the consequences of fluctuating selection pressures on the quantification of adaptive evolution using McDonald-Kreitman (MK) style approaches. In agreement with previous work, we show that fluctuating selection can generate evidence of adaptive evolution even when the expected strength of selection on a mutation is zero. However, we also find that the mutations, which contribute to both polymorphism and divergence tend, on average, to be positively selected during their lifetime, under fluctuating selection models. This is because mutations that fluctuate, by chance, to positive selected values, tend to reach higher frequencies in the population than those that fluctuate towards negative values. Hence the evidence of positive adaptive evolution detected under a fluctuating selection model by MK type approaches is genuine since fixed mutations tend to be advantageous on average during their lifetime. Never-the-less we show that methods tend to underestimate the rate of adaptive evolution when selection fluctuates

Relativistic Meson Spectroscopy and In-Medium Effects

We extend our earlier model of $q\bar q$ mesons using relativistic quasipotential (QP) wave equations to include open-flavor states and running quark-gluon coupling effects. Global fits to meson spectra are achieved with rms deviations from experiment of 43-50 MeV. We examine in-medium effects through their influence on the confining interaction and predict the confining strength at which the masses of certain mesons fall below the threshold of their dominant decay channel.Comment: 12 Pages, 2 Postscript figures (appended at the end with instructions, available also from [email protected]

The role of mutation rate variation and genetic diversity in the architecture of human disease

Background We have investigated the role that the mutation rate and the structure of genetic variation at a locus play in determining whether a gene is involved in disease. We predict that the mutation rate and its genetic diversity should be higher in genes associated with disease, unless all genes that could cause disease have already been identified. Results Consistent with our predictions we find that genes associated with Mendelian and complex disease are substantially longer than non-disease genes. However, we find that both Mendelian and complex disease genes are found in regions of the genome with relatively low mutation rates, as inferred from intron divergence between humans and chimpanzees, and they are predicted to have similar rates of non-synonymous mutation as other genes. Finally, we find that disease genes are in regions of significantly elevated genetic diversity, even when variation in the rate of mutation is controlled for. The effect is small nevertheless. Conclusions Our results suggest that gene length contributes to whether a gene is associated with disease. However, the mutation rate and the genetic architecture of the locus appear to play only a minor role in determining whether a gene is associated with disease

Potential for the use of reconstructed IASI radiances in the detection of atmospheric trace gases

Principal component (PC) analysis has received considerable attention as a technique for the extraction of meteorological signals from hyperspectral infra-red sounders such as the Infrared Atmospheric Sounding Interferometer (IASI) and the Atmospheric Infrared Sounder (AIRS). In addition to achieving substantial bit-volume reductions for dissemination purposes, the technique can also be used to generate reconstructed radiances in which random instrument noise has been reduced. Studies on PC analysis of hyperspectral infrared sounder data have been undertaken in the context of numerical weather prediction, instrument monitoring and geophysical variable retrieval, as well as data compression. This study examines the potential of PC analysis for chemistry applications. <br><br> A major concern in the use of PC analysis for chemistry is that the spectral features associated with trace gases may not be well represented in the reconstructed spectra, either due to deficiencies in the training set or due to the limited number of PC scores used in the radiance reconstruction. In this paper we show examples of reconstructed IASI radiances for several trace gases: ammonia, sulphur dioxide, methane and carbon monoxide. It is shown that care must be taken in the selection of spectra for the initial training set: an iterative technique, in which outlier spectra are added to a base training set, gives the best results. For the four trace gases examined, key features of the chemical signatures are retained in the reconstructed radiances, whilst achieving a substantial reduction in instrument noise. <br><br> A new regional re-transmission service for IASI is scheduled to start in 2010, as part of the EUMETSAT Advanced Retransmission Service (EARS). For this EARS-IASI service it is intended to include PC scores as part of the data stream. The paper describes the generation of the reference eigenvectors for this new service

Genome landscapes and bacteriophage codon usage

Across all kingdoms of biological life, protein-coding genes exhibit unequal usage of synonmous codons. Although alternative theories abound, translational selection has been accepted as an important mechanism that shapes the patterns of codon usage in prokaryotes and simple eukaryotes. Here we analyze patterns of codon usage across 74 diverse bacteriophages that infect E. coli, P. aeruginosa and L. lactis as their primary host. We introduce the concept of a `genome landscape,' which helps reveal non-trivial, long-range patterns in codon usage across a genome. We develop a series of randomization tests that allow us to interrogate the significance of one aspect of codon usage, such a GC content, while controlling for another aspect, such as adaptation to host-preferred codons. We find that 33 phage genomes exhibit highly non-random patterns in their GC3-content, use of host-preferred codons, or both. We show that the head and tail proteins of these phages exhibit significant bias towards host-preferred codons, relative to the non-structural phage proteins. Our results support the hypothesis of translational selection on viral genes for host-preferred codons, over a broad range of bacteriophages.Comment: 9 Color Figures, 5 Tables, 53 Reference

Temporal dynamics of aquatic communities and implications for pond conservation

Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

Virus Replication as a Phenotypic Version of Polynucleotide Evolution

In this paper we revisit and adapt to viral evolution an approach based on the theory of branching process advanced by Demetrius, Schuster and Sigmund ("Polynucleotide evolution and branching processes", Bull. Math. Biol. 46 (1985) 239-262), in their study of polynucleotide evolution. By taking into account beneficial effects we obtain a non-trivial multivariate generalization of their single-type branching process model. Perturbative techniques allows us to obtain analytical asymptotic expressions for the main global parameters of the model which lead to the following rigorous results: (i) a new criterion for "no sure extinction", (ii) a generalization and proof, for this particular class of models, of the lethal mutagenesis criterion proposed by Bull, Sanju\'an and Wilke ("Theory of lethal mutagenesis for viruses", J. Virology 18 (2007) 2930-2939), (iii) a new proposal for the notion of relaxation time with a quantitative prescription for its evaluation, (iv) the quantitative description of the evolution of the expected values in in four distinct "stages": extinction threshold, lethal mutagenesis, stationary "equilibrium" and transient. Finally, based on these quantitative results we are able to draw some qualitative conclusions.Comment: 23 pages, 1 figure, 2 tables. arXiv admin note: substantial text overlap with arXiv:1110.336

The assessment of science: the relative merits of post- publication review, the impact factor, and the number of citations

The assessment of scientific publications is an integral part of the scientific process. Here we investigate three methods of assessing the merit of a scientific paper: subjective post-publication peer review, the number of citations gained by a paper, and the impact factor of the journal in which the article was published. We investigate these methods using two datasets in which subjective post-publication assessments of scientific publications have been made by experts. We find that there are moderate, but statistically significant, correlations between assessor scores, when two assessors have rated the same paper, and between assessor score and the number of citations a paper accrues. However, we show that assessor score depends strongly on the journal in which the paper is published, and that assessors tend to over-rate papers published in journals with high impact factors. If we control for this bias, we find that the correlation between assessor scores and between assessor score and the number of citations is weak, suggesting that scientists have little ability to judge either the intrinsic merit of a paper or its likely impact. We also show that the number of citations a paper receives is an extremely error-prone measure of scientific merit. Finally, we argue that the impact factor is likely to be a poor measure of merit, since it depends on subjective assessment. We conclude that the three measures of scientific merit considered here are poor; in particular subjective assessments are an error-prone, biased, and expensive method by which to assess merit. We argue that the impact factor may be the most satisfactory of the methods we have considered, since it is a form of pre-publication review. However, we emphasise that it is likely to be a very error-prone measure of merit that is qualitative, not quantitative