Effects of Gestational Ozone Exposure on Privileged Placental and Brain Barrier Integrity

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects of ozone have been underexplored during gestation, when inducible teratogenesis during critical periods for development can result in catastrophic fetal outcomes, but also when more subtle impacts on placental supply can hamper sensitive developmental aspects such as in the brain. As the interface of maternal-fetal circulation, the placenta is a target organ of toxicological interest in hypertensive disorders of pregnancy such as preeclampsia. Moreover, the developing fetal blood-brain barrier (BBB) is underexplored, especially in relation to toxicological study. In the study at hand, proteomic analysis of amniotic fluid (AF) was assessed after exposure of pregnant Sprague-Dawley rats at two gestational timepoint representing critical periods during rat development. The AF proteome is an understudied window into the privileged amniotic environment and its response to toxicological stressors. Pregnant dams experienced a single 4-h exposure to ozone at GD10, a critical period of placental and BBB development, or at GD20, a period just prior to term and one of anatomical significance in brain development. AF samples were then collected at term for detailed proteomic analysis. Studies assessed: AF proteomic impacts between GD10 and GD20 time points; the differential response to 0.3 ppm or 1.0 ppm ozone dosage at GD20; and the overlap between AF proteomic and maternal serum proteomic responses to 0.3 ppm or 1.0 ppm GD20 ozone exposures. Subsequently, a plan was devised for targeted immunofluorescence microscopy assessments on the pathological effects within the placental and blood-brain barriers linked with the toxicological ozone response observed within the AF proteome. Overall, we identified 231 significant AF proteomic responses across all time points and ozone doses within the amniotic fluid. To our knowledge, this is the most comprehensive assessment of the AF proteome. Overlap was low between the AF proteomic responses to gestational exposure time or ozone dose, while considerably more consistent for maternal serum responses. The highly dynamic AF proteomic response to ozone, however, consistently related to extracellular matrix and vascular remodeling processes, many proteins with well-defined roles in the placenta and developing conceptus. Results with maternal serum indicated activation of the maternal compliment cascade system and systemic inflammation. Additionally, limited overlap between maternal serum and matched AF proteomes indicated the placenta or fetus as the primary contributors to the AF proteomic response to ozone. With placentation and cerebral angiogenesis just beginning in rat at GD10, we hypothesized a dramatic effect on these structures to be assessed with the devised immunofluorescence analysis. In placenta, we expect to observe conditions consistent with a hypertensive preeclamptic-like state. Our AF proteomic results showed significant fold changes in proteins associated with this disease such as galectin-1, MMP-2, TIMP-2, and osteopontin. In follow-up targeted analysis of these proteins in placenta, we expect to observe classic signs of preeclampsia and general placental dysfunction—shallow invasion of the maternal endometrial decidualized tissue layer and inadequate remodeling of the maternal spiral arteries resulting in inadequate fetal circulation. AF proteomic data also showed shifts in proteins important for vascular development in the fetal brain such as TGFβ, PKM and neuropilin-1. Thus, we devised follow-up studies to test for ozone-induced BBB barrier dysfunction within the fetal brain to include augmented tight-junction proteins, albumin leakage and promoted astrocytic and microglial reactivity proximal to the cerebrovasculature. Overall, the outlined studies have potential to demonstrate stark effects of critical-period ambient ozone exposure on the placenta and developing fetus

Einstellungen und Präferenzen deutscher Öko-Weinkonsumenten

Surveys across different countries elicited that consumers had positive perceptions regarding organic wine production and reported a willingness to pay a premium for organic wine. But how do consumers behave in real purchase situations? Data obtained from a panel of 30.000 households was used to analyse German organic wine consumers´ buying behaviour. Households´ attitudes regarding sustainable consumption were used for segmentation. The most promising consumer segment for organic wine from Germany is the cluster of consumers interested in organic and local food. A quality strategy is advised. Regarding the cluster interested in organic food, a comprehensive sustainability approach is recommended which would be most effectively for German red wine producers marketing their wine through retailers. Direct sellers are advised to focus on the consumer group interested in local food and to communicate the typicality of wine regions and benefits of organic production for the regional development. Concerning consumers of the cluster disinterested in sustainable food a discounter strategy would be most promising, particularly for organic rosé wine from Germany

Thermophysical modelling and parameter estimation of small solar system bodies via data assimilation

Deriving thermophysical properties such as thermal inertia from thermal infrared observations provides useful insights into the structure of the surface material on planetary bodies. The estimation of these properties is usually done by fitting temperature variations calculated by thermophysical models to infrared observations. For multiple free model parameters, traditional methods such as Least-Squares fitting or Markov-Chain Monte-Carlo methods become computationally too expensive. Consequently, the simultaneous estimation of several thermophysical parameters together with their corresponding uncertainties and correlations is often not computationally feasible and the analysis is usually reduced to fitting one or two parameters. Data assimilation methods have been shown to be robust while sufficiently accurate and computationally affordable even for a large number of parameters. This paper will introduce a standard sequential data assimilation method, the Ensemble Square Root Filter, to thermophysical modelling of asteroid surfaces. This method is used to re-analyse infrared observations of the MARA instrument, which measured the diurnal temperature variation of a single boulder on the surface of near-Earth asteroid (162173) Ryugu. The thermal inertia is estimated to be $295 \pm 18$ $\mathrm{J\,m^{-2}\,K^{-1}\,s^{-1/2}}$, while all five free parameters of the initial analysis are varied and estimated simultaneously. Based on this thermal inertia estimate the thermal conductivity of the boulder is estimated to be between 0.07 and 0.12 $\mathrm{W\,m^{-1}\,K^{-1}}$ and the porosity to be between 0.30 and 0.52. For the first time in thermophysical parameter derivation, correlations and uncertainties of all free model parameters are incorporated in the estimation procedure which is more than 5000 times more efficient than a comparable parameter sweep

On the Critical Temperature of Non-Periodic Ising Models on Hexagonal Lattices

The critical temperature of layered Ising models on triangular and honeycomb lattices are calculated in simple, explicit form for arbitrary distribution of the couplings.Comment: to appear in Z. Phys. B., 8 pages plain TEX, 1 figure available upon reques

Higher homotopy groups of complements of complex hyperplane arrangements

We generalize results of Hattori on the topology of complements of hyperplane arrangements, from the class of generic arrangements, to the much broader class of hypersolvable arrangements. We show that the higher homotopy groups of the complement vanish in a certain combinatorially determined range, and we give an explicit Z\pi_1-module presentation of \pi_p, the first non-vanishing higher homotopy group. We also give a combinatorial formula for the \pi_1-coinvariants of \pi_p. For affine line arrangements whose cones are hypersolvable, we provide a minimal resolution of \pi_2, and study some of the properties of this module. For graphic arrangements associated to graphs with no 3-cycles, we obtain information on \pi_2, directly from the graph. The \pi_1-coinvariants of \pi_2 may distinguish the homotopy 2-types of arrangement complements with the same \pi_1, and the same Betti numbers in low degrees.Comment: 24 pages, 3 figure

Resolving vibrational from electronic coherences in two-dimensional electronic spectroscopy: The role of the laser spectrum

The observation of coherent quantum effects in photosynthetic light-harvesting complexes prompted the question whether quantum coherence could be exploited to improve the efficiency in new energy materials. The detailed characterization of coherent effects relies on sensitive methods such as two-dimensional electronic spectroscopy (2D-ES). However, the interpretation of the results produced by 2D-ES is challenging due to the many possible couplings present in complex molecular structures. In this work, we demonstrate how the laser spectral profile can induce electronic coherence-like signals in monomeric chromophores, potentially leading to data misinterpretation. We argue that the laser spectrum acts as a filter for certain coherence pathways and thus propose a general method to differentiate vibrational from electronic coherences

Rhodopsin Expression Level Affects Rod Outer Segment Morphology and Photoresponse Kinetics

Background: The retinal rod outer segment is a sensory cilium that is specialized for the conversion of light into an electrical signal. Within the cilium, up to several thousand membranous disks contain as many as a billion copies of rhodopsin for efficient photon capture. Disks are continually turned over, requiring the daily synthesis of a prodigious amount of rhodopsin. To promote axial diffusion in the aqueous cytoplasm, the disks have one or more incisures. Across vertebrates, the range of disk diameters spans an order of magnitude, and the number and length of the incisures vary considerably, but the mechanisms controlling disk architecture are not well understood. The finding that transgenic mice overexpressing rhodopsin have enlarged disks lacking an incisure prompted us to test whether lowered rhodopsin levels constrain disk assembly. Methodology/Principal Findings: The structure and function of rods from hemizygous rhodopsin knockout (R+/−) mice with decreased rhodopsin expression were analyzed by transmission electron microscopy and single cell recording. R+/− rods were structurally altered in three ways: disk shape changed from circular to elliptical, disk surface area decreased, and the single incisure lengthened to divide the disk into two sections. Photocurrent responses to flashes recovered more rapidly than normal. A spatially resolved model of phototransduction indicated that changes in the packing densities of rhodopsin and other transduction proteins were responsible. The decrease in aqueous outer segment volume and the lengthened incisure had only minor effects on photon response amplitude and kinetics. Conclusions/Significance: Rhodopsin availability limits disk assembly and outer segment girth in normal rods. The incisure may buffer the supply of structural proteins needed to form larger disks. Decreased rhodopsin level accelerated photoresponse kinetics by increasing the rates of molecular collisions on the membrane. Faster responses, together with fewer rhodopsins, combine to lower overall sensitivity of R+/− rods to light