Physiogenomic resources for rat models of heart, lung and blood disorders

Cardiovascular disorders are influenced by genetic and environmental factors. The TIGR rodent expression web-based resource (TREX) contains over 2,200 microarray hybridizations, involving over 800 animals from 18 different rat strains. These strains comprise genetically diverse parental animals and a panel of chromosomal substitution strains derived by introgressing individual chromosomes from normotensive Brown Norway (BN/NHsdMcwi) rats into the background of Dahl salt sensitive (SS/JrHsdMcwi) rats. The profiles document gene-expression changes in both genders, four tissues (heart, lung, liver, kidney) and two environmental conditions (normoxia, hypoxia). This translates into almost 400 high-quality direct comparisons (not including replicates) and over 100,000 pairwise comparisons. As each individual chromosomal substitution strain represents on average less than a 5% change from the parental genome, consomic strains provide a useful mechanism to dissect complex traits and identify causative genes. We performed a variety of data-mining manipulations on the profiles and used complementary physiological data from the PhysGen resource to demonstrate how TREX can be used by the cardiovascular community for hypothesis generation.     

The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis

The zinc finger of the cerebellum gene (ZIC) discovered in Drosophila melanogaster (odd-paired) has five homologs in Xenopus, chicken, mice, and humans, and seven in zebrafish. This pattern of gene copy expansion is accompanied by a divergence in gene and protein structure, suggesting that Zic family members share some, but not all, functions. ZIC genes are implicated in neuroectodermal development and neural crest cell induction. All share conserved regions encoding zinc finger domains, however their heterogeneity and specification remain unexplained. In this review, the evolution, structure, and expression patterns of the ZIC homologs are described; specific functions attributable to individual family members are supported. A review of data from functional studies in Xenopus and murine models suggest that ZIC genes encode multifunctional proteins operating in a context-specific manner to drive critical events during embryogenesis. The identification of ZIC mutations in congenital syndromes highlights the relevance of these genes in human development.     

A ground-based transmission spectrum of the super-Earth exoplanet GJ 1214b

In contrast to planets with masses similar to that of Jupiter and higher, the bulk compositions of planets in the so-called super-Earth regime (masses 2-10 times that of the Earth) cannot be uniquely determined from a measurement of mass and radius alone. For these planets, there is a degeneracy between the mass and composition of both the interior and a possible atmosphere in theoretical models. The recently discovered transiting super-Earth exoplanet GJ 1214b is one example of this problem. Three distinct models for the planet that are consistent with its mass and radius have been suggested. Breaking the degeneracy between these models requires obtaining constraints on the planet's atmospheric composition. Here we report a ground-based measurement of the transmission spectrum of GJ 1214b between wavelengths of 780 and 1,000?nm. The lack of features in this spectrum rules out (at 4.9σ confidence) cloud-free atmospheres composed primarily of hydrogen. If the planet's atmosphere is hydrogen-dominated, then it must contain clouds or hazes that are optically thick at the observed wavelengths at pressures less than 200?mbar. Alternatively, the featureless transmission spectrum is also consistent with the presence of a dense, water vapour atmosphere.     

Evidence from the Pacific troposphere for large global sources of oxygenated organic compounds

The presence of oxygenated organic compounds in the troposphere strongly influences key atmospheric processes. Such oxygenated species are, for example, carriers of reactive nitrogen and are easily photolysed, producing free radicals-and so influence the oxidizing capacity and the ozone-forming potential of the atmosphere-and may also contribute significantly to the organic component of aerosols. But knowledge of the distribution and sources of oxygenated organic compounds, especially in the Southern Hemisphere, is limited. Here we characterize the tropospheric composition of oxygenated organic species, using data from a recent airborne survey conducted over the tropical Pacific Ocean (30 degrees N to 30 degrees S). Measurements of a dozen oxygenated chemicals (carbonyls, alcohols, organic nitrates, organic pernitrates and peroxides), along with several C2-C8 hydrocarbons, reveal that abundances of oxygenated species are extremely high, and collectively, oxygenated species are nearly five times more abundant than non-methane hydrocarbons in the Southern Hemisphere. Current atmospheric models are unable to correctly simulate these findings, suggesting that large, diffuse, and hitherto-unknown sources of oxygenated organic compounds must therefore exist. Although the origin of these sources is still unclear, we suggest that oxygenated species could be formed via the oxidation of hydrocarbons in the atmosphere, the photochemical degradation of organic matter in the oceans, and direct emissions from terrestrial vegetation.     

The M-superfamily of conotoxins: a review

The focus of this review is the M-superfamily of Conus venom peptides. Disulfide rich peptides belonging to the M-superfamily have three loop regions and the cysteine arrangement: CC–C–C–CC, where the dashes represent loops one, two, and three, respectively. Characterization of M-superfamily peptides has demonstrated that diversity in cystine connectivity occurs between different branches of peptides even though the cysteine pattern remains consistent. This superfamily is subdivided into five branches, M-1 through M-5, based on the number of residues in the third loop region, between the fourth and fifth cysteine residues. M-superfamily peptides appear to be ubiquitous in Conus venom. They are largely unexplained in indigenous biological function, and they represent an active area of research within the scientific community.     

Damage-associated molecular patterns and their receptors in upper airway pathologies

Inflammation of the nasal (rhinitis) and sinus mucosa (sinusitis) are prevalent medical conditions of the upper airways that are concurrent in many patients; hence the terminology “rhinosinusitis”. The disease status is further defined to be “chronic” in case symptoms persist for more than 12 weeks without resolution. A diverse spectrum of external factors including viral and bacterial insults together with epithelial barrier malfunctions could be implicated in the chronicity of the inflammatory responses in chronic rhinosinusitis (CRS). However, despite massive research efforts in an attempt to unveil the pathophysiology, the exact reason for a lack of resolution still remains poorly understood. A novel set of molecules that could be implicated in sustaining the inflammatory reaction may be found within the host itself. Indeed, besides mediators of inflammation originating from outside, some endogenous intracellular and/or extracellular matrix (ECM) components from the host can be released into the extracellular space upon damage induced during the initial inflammatory reaction where they gain functions distinct from those during normal physiology. These “host-self” molecules are known to modulate inflammatory responses under pathological conditions, potentially preventing resolution and contributing to the development of chronic inflammation. These molecules are collectively classified as damage-associated molecular patterns (DAMPs). This review summarizes the current knowledge regarding DAMPs in upper airway pathologies, also covering those that were previously investigated for their intracellular and/or ECM functions often acting as an antimicrobial agent or implicated in tissue/cell homeostasis, and for which their function as a danger signaling molecule was not assessed. It is, however, of importance to assess these molecules again from a point of view as a DAMP in order to further unravel the pathogenesis of CRS.     

Reinterpretation of the ultrastructure of cartilage matrix.

The epiphyseal cartilage from new-born mouse was treated with collagenase in two ways: either before fixation or after glutaraldehyde fixation. The electron dense granules of the matrix were not seen in the micrographs of cartilage treated with collagenase before fixation. It is concluded that collagen plays a definite role in the formation of the granules at the time of tissue fixation and that the granules are fixation artifacts.     

Observations expérimentales sur l'apnée acapnique chez le Chien

Summary Suppression of the chemo-receptors of the carotid sinus and aorta æreas prolongs the acapnic apnea markedly. Animals deprived of their chemo-receptors may even die in apnea.During hyperventilation, the expiratory position of the thorax increases. During the acapnic apnea the inspiratory position returns progressively to normal. During hyperventilation and acapnic apnea, rhythmic changes occur in the tonus of the respiratory muscles. These changes in tonus occur in normal animals as well as in animals deprived of their chemo-receptors and vagi nerves.In normal dogs, hyperventilation and acapnea do not induce a fall in arterial blood pressure. Arterial hypotension occurs, however, during hyperventilation in dogs deprived of their carotid sinus and aortic innervation. During acapnic apnea, the arterial blood pressure rises in animals deprived of their carotid sinus and aortic nerves. A secondary fall of arterial pressure occurs during prolonged acapnic apnea in these animals.