Immunology in the Clinic Review Series ; focus on host responses : invariant natural killer T cell activation following transplantation

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Allergy, Metabolic Diseases, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses. Invariant natural killer T (iNKT) cells have been shown to play a key role in the regulation of immunity in health and disease. However, iNKT cell responses have also been found to influence both rejection and the induction of tolerance following transplantation of allogeneic cells or organs. Although a number of mechanisms have been identified that lead to iNKT cell activation, how iNKT cells are activated following transplantation remains unknown. This review will attempt to identify potential mechanisms of iNKT cell activation in the context of transplantation by applying knowledge garnered from other disease situations. Furthermore, we put forward a novel mechanism of iNKT cell activation which we believe may be the dominant mechanism responsible for iNKT activation in this setting, i.e. bystander activation by interleukin-2 secreted by recently activated conventional T cells

Maximum principle and mutation thresholds for four-letter sequence evolution

A four-state mutation-selection model for the evolution of populations of DNA-sequences is investigated with particular interest in the phenomenon of error thresholds. The mutation model considered is the Kimura 3ST mutation scheme, fitness functions, which determine the selection process, come from the permutation-invariant class. Error thresholds can be found for various fitness functions, the phase diagrams are more interesting than for equivalent two-state models. Results for (small) finite sequence lengths are compared with those for infinite sequence length, obtained via a maximum principle that is equivalent to the principle of minimal free energy in physics.Comment: 25 pages, 16 figure

Active flow control systems architectures for civil transport aircraft

Copyright @ 2010 American Institute of Aeronautics and AstronauticsThis paper considers the effect of choice of actuator technology and associated power systems architecture on the mass cost and power consumption of implementing active flow control systems on civil transport aircraft. The research method is based on the use of a mass model that includes a mass due to systems hardware and a mass due to the system energy usage. An Airbus A320 aircraft wing is used as a case-study application. The mass model parameters are based on first-principle physical analysis of electric and pneumatic power systems combined with empirical data on system hardware from existing equipment suppliers. Flow control methods include direct fluidic, electromechanical-fluidic, and electrofluidic actuator technologies. The mass cost of electrical power distribution is shown to be considerably less than that for pneumatic systems; however, this advantage is reduced by the requirement for relatively heavy electrical power management and conversion systems. A tradeoff exists between system power efficiency and the system hardware mass required to achieve this efficiency. For short-duration operation the flow control solution is driven toward lighter but less power-efficient systems, whereas for long-duration operation there is benefit in considering heavier but more efficient systems. It is estimated that a practical electromechanical-fluidic system for flow separation control may have a mass up to 40% of the slat mass for a leading-edge application and 5% of flap mass for a trailing-edge application.This work is funded by the Sixth European Union Framework Programme as part of the AVERT project (Contract No. AST5-CT-2006-030914

Nocardia kroppenstedtii sp. nov., a novel actinomycete isolated from a lung transplant patient with a pulmonary infection

An actinomycete, strain N1286T, isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. It was most closely related to Nocardia farcinica DSM 43665T (99.8% gene similarity) but was distinguished from the latter by a low level of DNA:DNA relatedness. These strains were also distinguished by a broad range of phenotypic properties. On the basis of these data, it is proposed that isolate N1286T (=DSM 45810T = NCTC 13617T) should be classified as the type strain of a new Nocardia species for which the name Nocardia kroppenstedtii is proposed

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Developing and applying heterogeneous phylogenetic models with XRate

Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART .Comment: 34 pages, 3 figures, glossary of XRate model terminolog

Fast computation of distance estimators

BACKGROUND: Some distance methods are among the most commonly used methods for reconstructing phylogenetic trees from sequence data. The input to a distance method is a distance matrix, containing estimated pairwise distances between all pairs of taxa. Distance methods themselves are often fast, e.g., the famous and popular Neighbor Joining (NJ) algorithm reconstructs a phylogeny of n taxa in time O(n(3)). Unfortunately, the fastest practical algorithms known for Computing the distance matrix, from n sequences of length l, takes time proportional to l·n(2). Since the sequence length typically is much larger than the number of taxa, the distance estimation is the bottleneck in phylogeny reconstruction. This bottleneck is especially apparent in reconstruction of large phylogenies or in applications where many trees have to be reconstructed, e.g., bootstrapping and genome wide applications. RESULTS: We give an advanced algorithm for Computing the number of mutational events between DNA sequences which is significantly faster than both Phylip and Paup. Moreover, we give a new method for estimating pairwise distances between sequences which contain ambiguity Symbols. This new method is shown to be more accurate as well as faster than earlier methods. CONCLUSION: Our novel algorithm for Computing distance estimators provides a valuable tool in phylogeny reconstruction. Since the running time of our distance estimation algorithm is comparable to that of most distance methods, the previous bottleneck is removed. All distance methods, such as NJ, require a distance matrix as input and, hence, our novel algorithm significantly improves the overall running time of all distance methods. In particular, we show for real world biological applications how the running time of phylogeny reconstruction using NJ is improved from a matter of hours to a matter of seconds

Infiltration efficiency and subsurface water processes of a sustainable drainage system and consequences to flood management

With increased intensity rainfall events globally and urban expansion decreasing permeable surfaces, there is an increasing problem of urban flooding. This study aims to better understand rainfall infiltration into a Sustainable Drainage System (SuDS) permeable pavement, compared with an adjacent Green Area of made ground, in relationship to groundwater levels below both areas. Both areas were instrumented with soil water content and matric potential sensors and four shallow boreholes were instrumented with groundwater level sensors. Surface infiltration rates were measured using a double‐ring infiltrometer. Results showed that average infiltration rates of the SuDS (1,925 mm/hr) were significantly higher than the Green Area (56 mm/hr). The SuDS was well designed to transfer rainfall rapidly to the aquifer below, where groundwater levels rapidly rose within 1 hr of a 1 in 30 year event (32.8 mm/hr). In comparison, soil compaction of the made ground Green Area decreased infiltration rates, but still enabled the majority of rainfall events to infiltrate. The aquifer below the Green Area responded more slowly, as lower matrix potentials facilitated water retention in the soil profile, slowing water draining to the aquifer. This work reiterates the importance of ensuring a 1 m separation depth between the base of the SuDS infiltration zone and aquifer depth