MMP-9, TIMP-1 and inflammatory cells in sputum from COPD patients during exacerbation

Background

Irreversible airflow obstruction in Chronic Obstructive Pulmonary Disease (COPD) is thought to result from airway remodelling associated with aberrant inflammation. Patients who experience frequent episodes of acute deterioration in symptoms and lung function, termed exacerbations, experience a faster decline in their lung function, and thus over time greater disease severity However the mechanisms by which these episodes may contribute to decreased lung function are poorly understood.This study has prospectively examined changes in sputum levels of inflammatory cells, MMP-9 and TIMP-1 during exacerbations comparing with paired samples taken prior to exacerbation.

Methods

Nineteen COPD patients ((median, [IQR]) age 69 [63 to 74], forced expiratory volume in one second (FEV1) 1.0 [0.9 to1.2], FEV1% predicted 37.6 [27.3 to 46.2]) provided sputa at exacerbation. Of these, 12 were paired with a samples collected when the patient was stable, a median 4 months [2 to 8 months] beforehand.

Results

MMP-9 levels increased from 10.5 μg/g [1.2 to 21.1] prior to exacerbation to 17.1 μg/g [9.3 to 48.7] during exacerbation (P < 0.01). TIMP-1 levels decreased from 3.5 μg/g [0.6 to 7.8] to 1.5 μg/g [0.3 to 4.9] (P = 0.16). MMP-9/TIMP-1 Molar ratio significantly increased from 0.6 [0.2 to 1.1] to 3.6 [2.0 to 25.3] (P < 0.05). Neutrophil, eosinophil and lymphocyte counts all showed significant increase during exacerbation compared to before (P < 0.05). Macrophage numbers remained level. MMP-9 levels during exacerbation showed highly significant correlation with both neutrophil and lymphocyte counts (Rho = 0.7, P < 0.01).

Conclusion

During exacerbation, increased inflammatory burden coincides with an imbalance of the proteinase MMP-9 and its cognate inhibitor TIMP-1. This may suggest a pathway connecting frequent exacerbations with lung function decline.     

Surnames in Argentina: a population study through isonymy

In order to study the isonymic structure of Argentina, the surname distributions of 22.6 million electors registered for the year 2001 were analyzed in the 24 districts (distritos) and 541 municipalities (municipios) of the country. The number of different surnames found was 414,441. Matrices of isonymic distances between districts were constructed and tested for correlation with the geographic distance between the capital towns of the districts. We found that, for the whole of Argentina, Euclidean distance was correlated with the log of geographic distance (r=0.480+/- 0.067). A dendrogram of the 24 regions was built from the matrix of Euclidean distances, using the UPGMA method. The clusters identified by the dendrogram are coincident with conterminous geographical regions of the country. Random inbreeding calculated from isonymy, F(ST), was highest in La Rioja, Corrientes, and Santiago del Estero. It was lowest in the area of Buenos Aires and in the north-central region of Santa Fé. Average Fisher's alpha for municipalities was 358; for districts, it was 422; and for Argentina as a unit, it was 602. The geographical distribution of alpha in 541 municipalities, high in the east and lower in the west of the country, is compatible with the settlement in the 20th century of subsequent waves of immigrants moving from the North Atlantic coast toward the foot of the Andes and toward the south. The present structure of Argentina indicates that migration dominates over drift.     

Identification of volatile emissions from Platypus mutatus (=sulcatus) (Coleoptera: Platypodidae) and their behavioral activity

We report here the identification and behavioral activity of volatile compounds emitted by male Platypus mutatus (=sulcatus) Chapuis while boring galleries in living poplar, Populus deltoides Marshall, trees. Headspace analysis using solid phase microextraction techniques showed the presence of 6-methyl-5-hepten-2-ol (sulcatol) and 6-methyl-5-hepten-2-one (sulcatone). Only one enantiomer of sulcatol, retusol, was found to be part of the volatile emission. Behavioral assays showed that females are more attracted than males to galleries with boring males inside. Both sulcatol and sulcatone elicited electroantennographic responses by female P. mutatus. Furthermore, behavioral bioassays showed that both sulcatol and sulcatone elicit behaviorally attractive responses by females. These results suggest that male P. mutatus releases a sex pheromone composed mainly of retusol and sulcatone.     

The European Renal Genome Project: An Integrated Approach Towards Understanding the Genetics of Kidney Development and Disease

Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics     

The ontogeny of the spinning apparatus of Tengella perfuga (Araneae: Zoropsidae)

Silk is the most recognizable trait of spiders, and silk use has changed throughout spider evolutionary history. While morphology of the adult silk spigot has been a useful character for systematics, few studies have examined the ontogeny of the spinning apparatus, and none of these included cribellate spiders. Here, we report the first published full ontogeny of the spinning apparatus of a cribellate spider, Tengella perfuga. We found the presence of expected spigots: major ampullate gland and piriform gland spigots on the anterior lateral spinneret, minor ampullate gland and aciniform gland spigots on the posterior median spinneret, and aciniform gland spigots on the posterior lateral spinneret. Females, but not males, possessed cylindrical gland spigots on both the posterior median and lateral spinnerets. Spiderlings did not possess a functioning cribellum until the third instar. The cribellum grew with increasing numbers of spigots, but functionality was lost in adult males. Most intriguingly, second instars possessed a distinct triad of pre‐spigots on the posterior lateral spinneret. From the third instar onward, these structures formed the modified spigot along with two flanking spigots (in females) or formed nubbins (in males). We suggest that the modified spigot serves as the source of axial lines in the cribellate silk produced in T. perfuga. We also compare spigot ontogeny from previous studies of ecribellate spiders. These comparisons warrant further exploration using the recent spider tree of life in a phylogenetic comparative analysis of spigot ontogeny datasets, which could yield evidence for homologous spigots across the Araneomorphae, notably the Araneoidea and the Retrolateral Tibial Apophysis (RTA) clades.     

Phylogenetic inference: how much evolutionary history is knowable?

In order to reconstruct phylogenetic trees from extremely dissimilar sequences it is necessary to estimate accurately the extent of sequence divergence. In this paper a new method of sequence analysis, Markov triple analysis, is developed for determining the relative frequencies of nucleotide substitutions within the three branches of a three-taxon dendrogram. Assuming that nucleotide sites are independently and identically distributed and assuming a Markov model for nucleotide (or protein) evolution, it is shown that the unique Markov matrices can be reconstructed given only the joint probability distribution relating three taxa. (In the much simpler case involving only two taxa and two character states, Markov matrices can also be reconstructed, provided symmetry assumptions are placed on the elements of the matrices.) The method is illustrated using sequence data from the combined first and second codon positions derived from complete human, mouse, and cow mitochondrial sequences.      

DNA hybridization evidence for the principal lineages of hummingbirds (Aves:Trochilidae)

The spectacular evolutionary radiation of hummingbirds (Trochilidae) has served as a model system for many biological studies. To begin to provide a historical context for these investigations, we generated a complete matrix of DNA hybridization distances among 26 hummingbirds and an outgroup swift (Chaetura pelagica) to determine the principal hummingbird lineages. FITCH topologies estimated from symmetrized delta TmH-C values and subjected to various validation methods (bootstrapping, weighted jackknifing, branch length significance) indicated a fundamental split between hermit (Eutoxeres aquila, Threnetes ruckeri; Phaethornithinae) and nonhermit (Trochilinae) hummingbirds, and provided strong support for six principal nonhermit clades with the following branching order: (1) a predominantly lowland group comprising caribs (Eulampis holosericeus) and relatives (Androdon aequatorialis and Heliothryx barroti) with violet-ears (Colibri coruscans) and relatives (Doryfera ludovicae); (2) an Andean-associated clade of highly polytypic taxa (Eriocnemis, Heliodoxa, and Coeligena); (3) a second endemic Andean clade (Oreotrochilus chimborazo, Aglaiocercus coelestis, and Lesbia victoriae) paired with thorntails (Popelairia conversii); (4) emeralds and relatives (Chlorostilbon mellisugus, Amazilia tzacatl, Thalurania colombica, Orthorhyncus cristatus and Campylopterus villaviscensio); (5) mountain-gems (Lampornis clemenciae and Eugenes fulgens); and (6) tiny bee-like forms (Archilochus colubris, Myrtis fanny, Acestrura mulsant, and Philodice mitchellii). Corresponding analyses on a matrix of unsymmetrized delta values gave similar support for these relationships except that the branching order of the two Andean clades (2, 3 above) was unresolved. In general, subsidiary relationships were consistent and well supported by both matrices, sometimes revealing surprising associations between forms that differ dramatically in plumage and bill morphology. Our results also reveal some basic aspects of hummingbird ecologic and morphologic evolution. For example, most of the diverse endemic Andean assemblage apparently comprises two genetically divergent clades, whereas the majority of North American hummingbirds belong a single third clade. Genetic distances separating some morphologically distinct genera (Oreotrochilus, Aglaiocercus, Lesbia; Myrtis, Acestrura, Philodice) were no greater than among congeneric (Coeligena) species, indicating that, in hummingbirds, morphological divergence does not necessarily reflect level of genetic divergence.