Hippocampal epigenetic changes in a mouse model of Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) refers to the neurological, developmental, and behavioural abnormalities arising from in utero ethanol exposure. These abnormities included attention deficit, anxiety, and learning and memory impairment persisting into adulthood. The molecular mechanisms of such persistent behavioural changes remain unknown and are an area of intense research. In this thesis, mice were exposed to ethanol during the third trimester equivalent, the peak of synaptic development. Following this exposure, genome-wide epigenetic and gene expression and changes in the hippocampus were assessed in adult (70 day old) mice. In the first experiment, genome-wide trimethylation of histone H3 at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) were assessed using chromatin immunoprecipitation (ChIP) microarray (ChIP-chip). Cell-cell signalling genes were enriched for changes in both methylations. It included the protocadherin (Pcdh) genes, which confer neuronal identity and may be important for synaptic development. Changes in methylation also occurred at imprinted genes and lipid-metabolism genes The second experiment assessed DNA methylation using methylated DNA immunoprecipitation (MeDIP) microarray (MeDIP-chip). The screen identified genes involved in peroxisome biogenesis, which metabolize lipids and generate free-radicals. This was also true when the histone and DNA methylation changes were considered together. Combined analysis of affected genes from each experiment implicated free-radical scavenging genes. Identification of this novel interplay between epigenetic and oxidative stress genes may provide insight into diagnostic or therapeutic interventions. In general, the results support a role of epigenetic mechanisms in long-term FASD phenotypes. Finally, the third experiment examined gene expression and miRNA microarrays identified 59 and 60 differentially expressed genes and miRNAs between ethanol-exposed and control mice. These genes primarily affect free radical scavenging genes. Differential expression of five genes in this pathway was confirmed with droplet digital PCR (ddPCR), including the transcription factor Tcf7l2 and the apoptosis regulator Casp3. The affected genes also included other oxidative stress proteins, olfactory receptors, and biosynthetic enzymes that may contribute to FASD-related abnormalities

Death Vegas Valley

My work explores hallucinatory landscapes of the US American West by using a combination of painting styles outside of the Western painting canon. I cross-reference painting and cinema, interweaving video, acrylic paint and the panorama to create a satirical homage to the history and present state of the USA. However, through an earnest devotion to the medium - both painting and cinema - I find my criticisms also yearn to hold onto a belief in a myth I know to be false. This is an American History conversation about artifice and consumerism through advertising. I use Las Vegas and the Mojave Desert as my metaphor. Las Vegas’ rapidly expanding population has displaced actual plants and animals to replace them with artificial sculptures of the desert cactus and coyote. This desert landscape occupies what was previously Mexico and before that Indigenous lands. TV and hallucinogens play a part in my work - as a means to tap into the psychological staticky holiness of the desert, and I use certain painting techniques to mimic the optical effects of these phenomena. These techniques reference my experience with theater backdrop painting and psychedelic movie posters as well as kitsch hobbyist landscape painting. My focus is the specific territory outside of the National Parks service, the government lands leased to mining companies and housing developers. These are the mystical desert tracts of spacious landscape, just as ecologically important to the whole, yet considered “not quite pretty enough” to warrant a National Park sign or roaming ranger

Radar-based Dynamic Occupancy Grid Mapping and Object Detection

Environment modeling utilizing sensor data fusion and object tracking is crucial for safe automated driving. In recent years, the classical occupancy grid map approach, which assumes a static environment, has been extended to dynamic occupancy grid maps, which maintain the possibility of a low-level data fusion while also estimating the position and velocity distribution of the dynamic local environment. This paper presents the further development of a previous approach. To the best of the author's knowledge, there is no publication about dynamic occupancy grid mapping with subsequent analysis based only on radar data. Therefore in this work, the data of multiple radar sensors are fused, and a grid-based object tracking and mapping method is applied. Subsequently, the clustering of dynamic areas provides high-level object information. For comparison, also a lidar-based method is developed. The approach is evaluated qualitatively and quantitatively with real-world data from a moving vehicle in urban environments. The evaluation illustrates the advantages of the radar-based dynamic occupancy grid map, considering different comparison metrics.Comment: Accepted to be published as part of the 23rd IEEE International Conference on Intelligent Transportation Systems (ITSC), Rhodes, Greece, September 20-23, 202

Quadrupole Magnet Design based on Genetic Multi-Objective Optimization

This work suggests to optimize the geometry of a quadrupole magnet by means of a genetic algorithm adapted to solve multi-objective optimization problems. To that end, a non-domination sorting genetic algorithm known as NSGA-III is used. The optimization objectives are chosen such that a high magnetic field quality in the aperture of the magnet is guaranteed, while simultaneously the magnet design remains cost-efficient. The field quality is computed using a magnetostatic finite element model of the quadrupole, the results of which are post-processed and integrated into the optimization algorithm. An extensive analysis of the optimization results is performed, including Pareto front movements and identification of best designs.Comment: 22 pages, 7 figure

The Influence of the 2006 Indonesian Biomass Burning Aerosols on Tropical Dynamics Studied with the GEOS-5 AGCM

The direct and semi-direct effects of aerosols produced by Indonesian biomass burning (BB) during August November 2006 on tropical dynamics have been examined using NASA's Goddard Earth Observing System, Version 5 (GEOS-5) atmospheric general circulation model (AGCM). The AGCM includes CO, which is transported by resolved and sub-grid processes and subject to a linearized chemical loss rate. Simulations were driven by two sets of aerosol forcing fields calculated offline, one that included Indonesian BB aerosol emissions and one that did not. In order to separate the influence of the aerosols from internal model variability, the means of two ten-member ensembles were compared. Diabatic heating from BB aerosols increased temperatures over Indonesia between 150 and 400 hPa. The higher temperatures resulted in strong increases in upward grid-scale vertical motion, which increased water vapor and CO over Indonesia. In October, the largest increases in water vapor were found in the mid-troposphere (~25%) while the largest increases in CO occurred just below the tropopause (80 ppbv or ~50%). Diabatic heating from the Indonesian BB aerosols caused CO to increase by 9% throughout the tropical tropopause layer in November and 5% in the lower stratosphere in December. The results demonstrate that aerosol heating plays an important role in the transport of BB pollution and troposphere-to-stratosphere transport. Changes in vertical motion and cloudiness induced by aerosol heating can also alter the transport and phase of water vapor in the upper troposphere/lower stratosphere

Long-Term Genomic and Epigenomic Dysregulation as a Consequence of Prenatal Alcohol Exposure: A Model for Fetal Alcohol Spectrum Disorders

There is abundant evidence that prenatal alcohol exposure leads to a range of behavioral and cognitive impairments, categorized under the term fetal alcohol spectrum disorders (FASDs). These disorders are pervasive in Western cultures and represent the most common preventable source of neurodevelopmental disabilities. The genetic and epigenetic etiology of these phenotypes, including those factors that may maintain these phenotypes throughout the lifetime of an affected individual, has become a recent topic of investigation. This review integrates recent data that has progressed our understanding FASD as a continuum of molecular events, beginning with cellular stress response and ending with a long-term footprint of epigenetic dysregulation across the genome. It reports on data from multiple ethanol-treatment paradigms in mouse models that identify changes in gene expression that occur with respect to neurodevelopmental timing of exposure and ethanol dose. These studies have identified patterns of genomic alteration that are dependent on the biological processes occurring at the time of ethanol exposure. This review also adds to evidence that epigenetic processes such as DNA methylation, histone modifications, and non-coding RNA regulation may underlie long-term changes to gene expression patterns. These may be initiated by ethanol-induced alterations to DNA and histone methylation, particularly in imprinted regions of the genome, affecting transcription which is further fine-tuned by altered microRNA expression. These processes are likely complex, genome-wide, and interrelated. The proposed model suggests a potential for intervention, given that epigenetic changes are malleable and may be altered by postnatal environment. This review accentuates the value of mouse models in deciphering the molecular etiology of FASD, including those processes that may provide a target for the ammelioration of this common yet entirely preventable disorder

DNA Methylation Differences in Monozygotic Twin Pairs Discordant for Schizophrenia Identifies Psychosis Related Genes and Networks

Background Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. Methods We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. Results The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; “cell death and survival” and a “cellular movement and immune cell trafficking”. These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. Conclusions The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia

Kyleo® - Ein neues Breitbandherbizid für den Einsatz auf der Stoppel

Kyleo® ist eine Coformulierung auf der Basis von 160 g/l 2,4-D (als Säure) und 240 g/l Glyphosat (MIPA Salz), die sich durch eine besonders schnelle und tiefgreifende Wirkung gegen perennierende Unkräuter, Ausfallraps und Ausfallgetreide auszeichnet. Mit 2,4-D als synthetischem Auxin und Glyphosat als EPSP Synthase-Hemmer werden zwei komplementäre Wirkstoffe aus unterschiedlichen Gruppen von Wirkungsmechanismen kombiniert. Die innovative Fertigformulierung mit 200 g/l Cocoalcylamin (FHS) ermöglicht trotz extrem unterschiedlicher pH-Ansprüche der Einzelwirkstoffe eine Kombination ohne Wirkungsverlust im Gegensatz zur Tankmischung.Generell zeigt Kyleo eine im Vergleich zu reinen Glyphosat-Formulierungen stark erhöhte Wirkungsgeschwindigkeit. Die Wirkung auf dikotyle Unkräuter in größeren Entwicklungsstadien wird durch die Kombination der beiden Wirkstoffe verbessert. Ausfallraps im 8-10 Blattstadium wird bereits mit 3 l/ha sicher erfasst, Ausfallgetreide ebenso. Auf Ausfallerbsen und -bohnen kann mit Hilfe der Coformulierung eine erheblich bessere Wirkung als mit den Soloprodukten und eine synergistische Wirkung gegenüber der Tankmischung erreicht werden. Auf Ackerkratzdistel (Cirsium arvense) wurde mit 3 l/ha eine 95 %ige Wirkung erzielt. Gegen den Ackerschachtelhalm (Equisetum arvense) werden vier Wochen nach der Anwendung Wirkungsgrade von 82 % mit 3 l/ha und 92 % mit 5 l/ha erreicht. Die Ackerwinde (Convolvulus arvense) wird mit 3 l/ha zu 88 %, mit 5 l/ha zu 100 % erfasst. Gegen die Quecke (Agropyron repens) wird mit 5 l/ha Kyleo ein Wirkungsgrad von 96 % erreicht.Durch sein breites Wirkungsspektrum und insbesondere die gute Wirkung gegen perennierende Arten, eignet sich Kyleo sehr gut für den Einsatz in Anbausystemen mit Minimalbodenbearbeitung, aber auch auf Gleisen, im Obstbau oder zur Grünlanderneuerung.Stichwörter: Ausfallgetreide, Ausfallraps, Breitbandherbizid, 2,4-D, Glyphosat, Kyleo, perennierende Unkräuter, Stoppel, WirkungsgeschwindigkeitKyleo® - A new broad spectrum herbicide for use on stubblesKyleo® is a coformulation of 160 g/l 2,4-D (as acid) and 240 g/l glyphosate (as MIPA salt), with rapid action and excellent efficacy against volunteer oilseed rape, cereals and perennial weeds. Two complementary active ingredients with different MOA are combined in an innovative coformulation using 200 g/l cocoalcylamin (adjuvant) to handle the extremely different ph requirements of the actives, avoiding a loss of efficacy that often appears using the tankmix of both.Volunteer oilseed rape at 8-10 leaf stage is controlled already with 3 l/ha, volunteer cereals as well. The efficacy against volunteer beans and peas is improved significantly versus the use of the actives and a synergistic effect can be observed compared to the tankmix of both. At 3 l/ha respectively 5 l/ha the control levels against Equisetum arvense reached 82 % and 95 %, against Convolvulus arvense 88 % respectively 100 % and against Agropyron repens 96 % with 5 l/ha.With its broad spectrum and the good efficacy against perennial weeds, Kyleo is an excellent option for for minimum tillage systems as well as for the use on railways, in orchards and for grassland renewal. Keywords: Broad spectrum, 2,4-D, glyphosate, herbicide, Kyleo, perennial weeds, rapid action, stubble, volunteer crop