Comparative genomic analysis of the odorant-binding protein family in 12 Drosophila genomes: purifying selection and birth-and-death evolution

Background: Chemoreception is a widespread mechanism that is involved in critical biologic processes, including individual and social behavior. The insect peripheral olfactory system comprises three major multigene families: the olfactory receptor (Or), the gustatory receptor (Gr), and the odorant-binding protein (OBP) families. Members of the latter family establish the first contact with the odorants, and thus constitute the first step in the chemosensory transduction pathway.Results: Comparative analysis of the OBP family in 12 Drosophila genomes allowed the identification of 595 genes that encode putative functional and nonfunctional members in extant species, with 43 gene gains and 28 gene losses (15 deletions and 13 pseudogenization events). The evolution of this family shows tandem gene duplication events, progressive divergence in DNA and amino acid sequence, and prevalence of pseudogenization events in external branches of the phylogenetic tree. We observed that the OBP arrangement in clusters is maintained across the Drosophila species and that purifying selection governs the evolution of the family; nevertheless, OBP genes differ in their functional constraints levels. Finally, we detect that the OBP repertoire evolves more rapidly in the specialist lineages of the Drosophila melanogaster group (D. sechellia and D. erecta) than in their closest generalists.Conclusion: Overall, the evolution of the OBP multigene family is consistent with the birth-and-death model. We also found that members of this family exhibit different functional constraints, which is indicative of some functional divergence, and that they might be involved in some of the specialization processes that occurred through the diversification of the Drosophila genus.

Procedure for human saphenous veins ex vivo perfusion and external reinforcement.

The mainstay of contemporary therapies for extensive occlusive arterial disease is venous bypass graft. However, its durability is threatened by intimal hyperplasia (IH) that eventually leads to vessel occlusion and graft failure. Mechanical forces, particularly low shear stress and high wall tension, are thought to initiate and to sustain these cellular and molecular changes, but their exact contribution remains to be unraveled. To selectively evaluate the role of pressure and shear stress on the biology of IH, an ex vivo perfusion system (EVPS) was created to perfuse segments of human saphenous veins under arterial regimen (high shear stress and high pressure). Further technical innovations allowed the simultaneous perfusion of two segments from the same vein, one reinforced with an external mesh. Veins were harvested using a no-touch technique and immediately transferred to the laboratory for assembly in the EVPS. One segment of the freshly isolated vein was not perfused (control, day 0). The two others segments were perfused for up to 7 days, one being completely sheltered with a 4 mm (diameter) external mesh. The pressure, flow velocity, and pulse rate were continuously monitored and adjusted to mimic the hemodynamic conditions prevailing in the femoral artery. Upon completion of the perfusion, veins were dismounted and used for histological and molecular analysis. Under ex vivo conditions, high pressure perfusion (arterial, mean = 100 mm Hg) is sufficient to generate IH and remodeling of human veins. These alterations are reduced in the presence of an external polyester mesh.

The hourglass and the early conservation models--co-existing patterns of developmental constraints in vertebrates.

Developmental constraints have been postulated to limit the space of feasible phenotypes and thus shape animal evolution. These constraints have been suggested to be the strongest during either early or mid-embryogenesis, which corresponds to the early conservation model or the hourglass model, respectively. Conflicting results have been reported, but in recent studies of animal transcriptomes the hourglass model has been favored. Studies usually report descriptive statistics calculated for all genes over all developmental time points. This introduces dependencies between the sets of compared genes and may lead to biased results. Here we overcome this problem using an alternative modular analysis. We used the Iterative Signature Algorithm to identify distinct modules of genes co-expressed specifically in consecutive stages of zebrafish development. We then performed a detailed comparison of several gene properties between modules, allowing for a less biased and more powerful analysis. Notably, our analysis corroborated the hourglass pattern at the regulatory level, with sequences of regulatory regions being most conserved for genes expressed in mid-development but not at the level of gene sequence, age, or expression, in contrast to some previous studies. The early conservation model was supported with gene duplication and birth that were the most rare for genes expressed in early development. Finally, for all gene properties, we observed the least conservation for genes expressed in late development or adult, consistent with both models. Overall, with the modular approach, we showed that different levels of molecular evolution follow different patterns of developmental constraints. Thus both models are valid, but with respect to different genomic features.

External Fluctuations in Front Propagation

We study the effects of external noise in a one-dimensional model of front propagation. Noise is introduced through the fluctuations of a control parameter leading to a multiplicative stochastic partial differential equation. Analytical and numerical results for the front shape and velocity are presented. The linear-marginal-stability theory is found to increase its range of validity in the presence of external noise. As a consequence noise can stabilize fronts not allowed by the deterministic equation.

Statistical Modeling of the Eye for Multimodal Treatment Planning for External Beam Radiation Therapy of Intraocular Tumors.

PURPOSE: Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors. METHODS AND MATERIALS: Manual and automatic segmentations were compared for 17 patients, based on head computed tomography (CT) volume scans. A 3D statistical shape model of the cornea, lens, and sclera as well as of the optic disc position was developed. Furthermore, an active shape model was built to enable automatic fitting of the eye model to CT slice stacks. Cross-validation was performed based on leave-one-out tests for all training shapes by measuring dice coefficients and mean segmentation errors between automatic segmentation and manual segmentation by an expert. RESULTS: Cross-validation revealed a dice similarity of 95% ± 2% for the sclera and cornea and 91% ± 2% for the lens. Overall, mean segmentation error was found to be 0.3 ± 0.1 mm. Average segmentation time was 14 ± 2 s on a standard personal computer. CONCLUSIONS: Our results show that the solution presented outperforms state-of-the-art methods in terms of accuracy, reliability, and robustness. Moreover, the eye model shape as well as its variability is learned from a training set rather than by making shape assumptions (eg, as with the spherical or elliptical model). Therefore, the model appears to be capable of modeling nonspherically and nonelliptically shaped eyes.

Juxtaposition of melt impregnation and high-temperature shear zones in the upper mantle; field and petrological constraints from the Lanzo peridotite (Northern Italy)

Results of a field and microstructural study between the northern and the central bodies of the Lanzo plagioclase peridotite massif (NW Italy) indicate that the spatial distribution of deformation is asymmetric across kilometre-scale mantle shear zones. The southwestern part of the shear zone (footwall) shows a gradually increasing degree of deformation from porphyroclastic peridotites to mylonite, whereas the northeastern part (hanging wall) quickly grades into weakly deformed peridotites. Discordant gabbroic and basaltic dykes are asymmetrically distributed and far more abundant in the footwall of the shear zone. The porphyroclastic peridotite displays porphyroclastic zones and domains of igneous crystallization whereas mylonites are characterized by elongated porphyroclasts, embedded between fine-grained, polycrystalline bands of olivine, plagioclase, clinopyroxene, orthopyroxene, spinel, rare titanian pargasite, and domains of recrystallized olivine. Two types of melt impregnation textures have been found: (1) clinopyroxene porphyroclasts incongruently reacted with migrating melt to form orthopyroxene plagioclase; (2) olivine porphyroclasts are partially replaced by interstitial orthopyroxene. The meltrock reaction textures tend to disappear in the mylonites, indicating that deformation in the mylonite continued under subsolidus conditions. The pyroxene chemistry is correlated with grain size. High-Al pyroxene cores indicate high temperatures (11001030C), whereas low-Al neoblasts display lower final equilibration temperatures (860C). The spinel Cr-number [molar Cr/(Cr Al)] and TiO2 concentrations show extreme variability covering almost the entire range known from abyssal peridotites. The spinel compositions of porphyroclastic peridotites from the central body are more variable than spinel from mylonite, mylonite with ultra-mylonite bands, and porphyroclastic rocks of the northern body. The spinel compositions probably indicate disequilibrium and would favour rapid cooling, and a faster exhumation of the central peridotite body, relative to the northern one. Our results indicate that melt migration and high-temperature deformation are juxtaposed both in time and space. Meltrock reaction may have caused grain-size reduction, which in turn led to localization of deformation. It is likely that melt-lubricated, actively deforming peridotites acted as melt focusing zones, with permeabilities higher than the surrounding, less deformed peridotites. Later, under subsolidus conditions, pinning in polycrystalline bands in the mylonites inhibited substantial grain growth and led to permanent weak zones in the upper mantle peridotite, with a permeability that is lower than in the weakly deformed peridotites. Such an inversion in permeability might explain why actively deforming, fine-grained peridotite mylonite acted as a permeability barrier and why ascending mafic melts might terminate and crystallize as gabbros along actively deforming shear zones. Melt-lubricated mantle shear zones provide a mechanism for explaining the discontinuous distribution of gabbros in oceancontinent transition zones, oceanic core complexes and ultraslow-spreading ridges.

Constraints on the permeability structure of alluvial aquifers from the poro-elastic inversion of multi-frequency P-wave velocity logs

We have explored the possibility of obtaining first-order permeability estimates for saturated alluvial sediments based on the poro-elastic interpretation of the P-wave velocity dispersion inferred from sonic logs. Modern sonic logging tools designed for environmental and engineering applications allow one for P-wave velocity measurements at multiple emitter frequencies over a bandwidth covering 5 to 10 octaves. Methodological considerations indicate that, for saturated unconsolidated sediments in the silt to sand range and typical emitter frequencies ranging from approximately 1 to 30 kHz, the observable velocity dispersion should be sufficiently pronounced to allow one for reliable first-order estimations of the permeability structure. The corresponding predictions have been tested on and verified for a borehole penetrating a typical surficial alluvial aquifer. In addition to multifrequency sonic logs, a comprehensive suite of nuclear and electrical logs, an S-wave log, a litholog, and a limited number laboratory measurements of the permeability from retrieved core material were also available. This complementary information was found to be essential for parameterizing the poro-elastic inversion procedure and for assessing the uncertainty and internal consistency of corresponding permeability estimates. Our results indicate that the thus obtained permeability estimates are largely consistent with those expected based on the corresponding granulometric characteristics, as well as with the available evidence form laboratory measurements. These findings are also consistent with evidence from ocean acoustics, which indicate that, over a frequency range of several orders-of-magnitude, the classical theory of poro-elasticity is generally capable of explaining the observed P-wave velocity dispersion in medium- to fine-grained seabed sediments

Ruling out coronary heart disease in primary care: external validation of a clinical prediction rule.

BACKGROUND: The Marburg Heart Score (MHS) aims to assist GPs in safely ruling out coronary heart disease (CHD) in patients presenting with chest pain, and to guide management decisions. AIM: To investigate the diagnostic accuracy of the MHS in an independent sample and to evaluate the generalisability to new patients. DESIGN AND SETTING: Cross-sectional diagnostic study with delayed-type reference standard in general practice in Hesse, Germany. METHOD: Fifty-six German GPs recruited 844 males and females aged ≥ 35 years, presenting between July 2009 and February 2010 with chest pain. Baseline data included the items of the MHS. Data on the subsequent course of chest pain, investigations, hospitalisations, and medication were collected over 6 months and were reviewed by an independent expert panel. CHD was the reference condition. Measures of diagnostic accuracy included the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, likelihood ratios, and predictive values. RESULTS: The AUC was 0.84 (95% confidence interval [CI] = 0.80 to 0.88). For a cut-off value of 3, the MHS showed a sensitivity of 89.1% (95% CI = 81.1% to 94.0%), a specificity of 63.5% (95% CI = 60.0% to 66.9%), a positive predictive value of 23.3% (95% CI = 19.2% to 28.0%), and a negative predictive value of 97.9% (95% CI = 96.2% to 98.9%). CONCLUSION: Considering the diagnostic accuracy of the MHS, its generalisability, and ease of application, its use in clinical practice is recommended.

The Upper Oligocene of Montgat (Catalan Coastal Ranges, Spain): new age constraints to the western Mediterranean Basin opening

The Oligocene deposits of Montgat are integrated in a small outcrop made up of Cenozoic and Mesozoic rocks located in the Garraf-Montnegre horst, close to the major Barcelona fault. The Oligocene of Montgat consists of detrital sediments of continental origin mainly deposited in alluvial fan environments; these deposits are folded and affected by thrusts and strike-slip faults. They can be divided in two lithostratigraphic units separated by a minor southwest-directed thrust: (i) the Turó de Montgat Unit composed of litharenites and lithorudites with high contents of quartz, feldspar, plutonic and limestone rock fragments; and (ii) the Pla de la Concòrdia Unit composed of calcilitharenites and calcilithorudites with high contents of dolosparite and dolomicrite rock fragments. The petrological composition of both units indicates that sediments were derived from the erosion of Triassic (Buntsandstein, Muschelkalk and Keuper facies), Jurassic and Lower Cretaceous rocks (Barremian to Aptian in age). Stratigraphic and petrological data suggest that these units correspond to two coalescent alluvial fans with a source area located northwestwards in the adjoining Collserola and Montnegre inner areas. Micromammal fossils (Archaeomys sp.) found in a mudstone layer of the Pla de la Concòrdia Unit assign a Chattian age (Late Oligocene) to the studied materials. Thus, the Montgat deposits are the youngest dated deposits affected by the contractional deformation that led to the development of the Catalan Intraplate Chain. Taking into account that the oldest syn-rift deposits in the Catalan Coastal Ranges are Aquitanian in age, this allows to precise that the change from a compressive to an extensional regime in this area took place during latest Oligocene-earliest Aquitanian times. This age indicates that the onset of crustal extension related to the opening of the western Mediterranean Basin started in southern France during latest Eocene-early Oligocene and propagated southwestward, affecting the Catalan Coastal Ranges and the northeastern part of the Valencia trough during the latest Chattian-earliest Aquitanian times.

Stochastic delay equations with non-negativity constraints driven by fractional Brownian motion

In this note we prove an existence and uniqueness result for the solution of multidimensional stochastic delay differential equations with normal reflection. The equations are driven by a fractional Brownian motion with Hurst parameter H > 1/2. The stochastic integral with respect to the fractional Brownian motion is a pathwise Riemann¿Stieltjes integral.

The Upper Oligocene of Montgat (Catalan Coastal Ranges, Spain): new age constraints to the western Mediterranean Basin opening

The Oligocene deposits of Montgat are integrated in a small outcrop made up of Cenozoic and Mesozoic rocks located in the Garraf-Montnegre horst, close to the major Barcelona fault. The Oligocene of Montgat consists of detrital sediments of continental origin mainly deposited in alluvial fan environments; these deposits are folded and affected by thrusts and strike-slip faults. They can be divided in two lithostratigraphic units separated by a minor southwest-directed thrust: (i) the Turó de Montgat Unit composed of litharenites and lithorudites with high contents of quartz, feldspar, plutonic and limestone rock fragments; and (ii) the Pla de la Concòrdia Unit composed of calcilitharenites and calcilithorudites with high contents of dolosparite and dolomicrite rock fragments. The petrological composition of both units indicates that sediments were derived from the erosion of Triassic (Buntsandstein, Muschelkalk and Keuper facies), Jurassic and Lower Cretaceous rocks (Barremian to Aptian in age). Stratigraphic and petrological data suggest that these units correspond to two coalescent alluvial fans with a source area located northwestwards in the adjoining Collserola and Montnegre inner areas. Micromammal fossils (Archaeomys sp.) found in a mudstone layer of the Pla de la Concòrdia Unit assign a Chattian age (Late Oligocene) to the studied materials. Thus, the Montgat deposits are the youngest dated deposits affected by the contractional deformation that led to the development of the Catalan Intraplate Chain. Taking into account that the oldest syn-rift deposits in the Catalan Coastal Ranges are Aquitanian in age, this allows to precise that the change from a compressive to an extensional regime in this area took place during latest Oligocene-earliest Aquitanian times. This age indicates that the onset of crustal extension related to the opening of the western Mediterranean Basin started in southern France during latest Eocene-early Oligocene and propagated southwestward, affecting the Catalan Coastal Ranges and the northeastern part of the Valencia trough during the latest Chattian-earliest Aquitanian times.

Radiometric age constraints on mineral growth, metamorphism, and tectonism of the Gummfluh klippe, Brianconnais domain of the Prealpes, Switzerland

A combined Ar-40/Ar-39, K/Ar, Rb/Sr and stable isotope study has been made of white micas from the Gummfluh klippe (Brianconnais domain of the Prealpes), Switzerland. The klippe consists mainly of Mesozoic to early Tertiary carbonate rocks metamorphosed from anchizonal to epizonal conditions. At the base of the klippe is a 10-50 m thick, ductilely deformed marble mylonite containing deformed authigenic quartz segregations. Stable isotope measurements of the coexisting calcite (deltaO-18SMOW=24.5) and quartz (deltaO-18SMOW=28.4) from the mylonite indicate relatively low temperatures (< 300-degreesC) during mylonitization. Analyses of white mica separates of varying size fractions from the mylonitic rocks by K/Ar and Rb/Sr techniques yield ages between 57 and 103 Ma. This variation is correlated with two parameters, the size of the mineral fraction, and the proportion of 2M1 (more phengitic) to 1M (more muscovitic) polytype in the sample. The K/Ar and Rb/Sr ages are generally younger in the smaller size fractions, which also containless 2M1 phengite. High precision Ar-40/Ar-39 age spectra from different size fractions of these micas record three distinct components, a small Hercynian component (ca. 200-300 Ma), a significant Eoalpine component (64-80 Ma) forming Ar-40/Ar-39 age plateaus, and a very minor Tertiary component (ca. 20-40 Ma). Characterization of the samples by SEM indicates the presence of two white mica populations, a coarser grained, deformed, detrital mica that probably corresponds to the 2M1 phengite and a finer grained neoformed 1M mica. Collectively these observations suggest that the Gummfluh samples contain a mixture of detrital phengites of Hercynian age together with neocrystallized muscovites grown during the late Eoalpine metamorphic event followed by minor argon loss during the Tertiary. The main geologic episode recorded in the Ar-40/Ar-39 age spectra of white micas in the mylonite is of Late Cretaceous/Early Tertiary age (64-80 Ma), representing the first reliable Eoalpine ages ever to be reported from the Prealpes. Contrary to tectonic models, the marble mylonite at the base of the Gummfluh klippe appears to be a Cretaceous thrust plane and not the thrust surface formed during transport of the klippe into its present position from the Penninic Alps during the Tertiary. The late Cretaceous thrust developed during marine sedimentation at a depth of 800 m below the seafloor at temperatures of approximately 280-degrees-C, facilitated by warm fluids along the tectonic discontinuity.