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Visual snow is the main symptom of visual snow syndrome, a disorder of predominantly visual disturbances initially described in patients without abnormalities on ancillary investigations. We present a case series of patients with visual snow in the setting of acute ischemic stroke. The first and second patient reported previous episodic visual snow with migraine attacks. The third patient experienced visual snow for the first time during the ischemic stroke. In the first patient, the ischemic stroke affected the right and left precuneus and the right lingual gyrus. In the second patient, the ischemic stroke was located in the left lingual gyrus, parts of the left fusiform and parahippocampal gyrus, left dorso-lateral thalamus, and left cerebellar hemisphere. In the third patient, occipital pole, trunk of the corpus callosum on the right, right paramedian pons, right cerebellar hemisphere, and vermis were affected. Our case series indicates that the symptom visual snow can be caused by vascular lesions in areas of visual processing. Because patients did not meet criteria for visual snow syndrome, dysfunction in the affected areas might only explain part of the complex pathophysiology of visual snow syndrome.

Die Gründe für die Abwanderung aus dem ländlichen Raum sind ebenso wie die Folgen vielfältig. Um entsprechende Gegenmaßnahmen ergreifen und auf die Bedürfnisse der Bewohnerinnen und Bewohner angemessen eingehen zu können, ist ein gemeinsamer Diskurs über die Zukunft ländlicher Räume notwendig. Durch eine entsprechende Bürgerbeteiligung und aktive Gestaltung der Lebensverhältnisse kann die Lebensqualität erhöht und ein Leben dort weiterhin ermöglicht werden. Damit auf die Wünsche und Bedürfnisse der Bürgerinnen und Bürger der ILE-Nationalparkgemeinden optimal und rechtzeitig eingegangen werden kann, haben sich fünf der sechs Gemeinden an einem Forschungsprojekt zum Thema Innenentwicklung beteiligt. Die Gemeinden Bayerisch-Eisenstein, Frauenau, Neuschönau, Spiegelau und St. Oswald-Riedlhütte haben dabei Unterstützung von der Professur für Regionale Geographie der Universität Passau und dem Amt für ländliche Entwicklung Niederbayern erhalten. Ziel des Projekts ist es, mit Hilfe einer umfangreichen Bürgerbeteiligung Handlungsempfehlungen für die Innenentwicklung in den Bereichen Nahversorgung, Wohnen, Öffentlicher Raum, Gesellschaftliche Teilhabe und Klimaschutz zu geben und so die Gemeinden zukunftsfähig und altersgerecht zu gestalten.

Additional file 1: Figures S1 to S6.

The aggregation of amyloid-β (Aβ) is postulated to be the crucial event in Alzheimer’s disease (AD). In particular, small neurotoxic Aβ oligomers are considered to be responsible for the development and progression of AD. Therefore, elimination of thesis oligomers represents a potential causal therapy of AD. Starting from the well-characterized D-enantiomeric peptide D3, we identified D3 derivatives that bind monomeric Aβ. The underlying hypothesis is that ligands bind monomeric Aβ and stabilize these species within the various equilibria with Aβ assemblies, leading ultimately to the elimination of Aβ oligomers. One of the hereby identified D-peptides, DB3, and a head-to-tail tandem of DB3, DB3DB3, were studied in detail. Both peptides were found to: (i) inhibit the formation of Thioflavin T-positive fibrils; (ii) bind to Aβ monomers with micromolar affinities; (iii) eliminate Aβ oligomers; (iv) reduce Aβ-induced cytotoxicity; and (v) disassemble preformed Aβ aggregates. The beneficial effects of DB3 were improved by DB3DB3, which showed highly enhanced efficacy. Our approach yielded Aβ monomer-stabilizing ligands that can be investigated as a suitable therapeutic strategy against AD.

The major transition to eusociality required the evolution of a switch to canalize development into either a reproductive or a helper, the nature of which is currently unknown. Following predictions from the ‘theory of facilitated variation’, we identify sex differentiation pathways as promising candidates because of their pre-adaptation to regulating development of complex phenotypes. We show that conserved core genes, including the juvenile hormone-sensitive master sex differentiation gene doublesex (dsx) and a krüppel homolog 2 (kr-h2) with putative regulatory function, exhibit both sex and morph-specific expression across life stages in the ant Cardiocondyla obscurior. We hypothesize that genes in the sex differentiation cascade evolved perception of alternative input signals for caste differentiation (i.e. environmental or genetic cues), and that their inherent switch-like and epistatic behavior facilitated signal transfer to downstream targets, thus allowing them to control differential development into morphological castes., Author Summary Division of labor into reproductive queens and helper workers in the societies of ants, bees and wasps is achieved by phenotypic plasticity, which allows individuals to embark on discrete developmental trajectories in response to variable signals. These signals can be genetic, epigenetic or environmental, thereby resembling the extreme variation in signals for sex determination across multicellular animals. We show that common developmental pathways downstream of these input signals, including the conserved sex differentiation gene doublesex, regulate sex and caste-specific phenotypic differentiation in the ant species Cardiocondyla obscurior. Many different mechanisms of gene regulation have been implicated in controlling caste-specific development in social insects but these all depend on a higher-level genetic switch. We propose that highly conserved hub genes such as dsx, which can translate variable input signals into large transcription differences using intermediate-level regulators, are tightly linked with the repeated evolutionary transition to eusociality and caste polyphenism.

It is generally discussed if evolutionary novelties are caused by novel genes or by cooption of existing genes and pathways. This thesis highlights de novo acquisition of novelty via endosymbiosis as well as novelty by combination of existing material through co-option of genes and by homologous recombination of the genome. Chapter 1 summarizes the present state of the art in the study of evolutionary novelty. The chapter introduces into the holobiont concept and the potential of endosymbiotic bacteria for host evolution. Moreover it gives an overview of sex determination systems in insects and an introduction into the conserved sex determination gene doublesex, which is investigated in Chapter 3 in detail. Furthermore, an overview of meiotic recombination and genetic linkage mapping is given, thereby providing an introduction for Chapter 4. The Chapter concludes with the introduction into the model organism Cardiocondyla obscurior and the ergatoid male morph, an evolutionary novelty of the genus Cardiocondyla. In Chapter 2 a novel endosymbiotic bacterium, "Candidatus Westeberhardia cardiocondylae", and its interaction with the host C. obscurior is described. Severe genome reduction and the localization in bacteriomes during the pupal stage strongly suggest a mutualistic nature of the symbiosis. Metabolic pathway analysis of the streamlined Westeberhardia genome together with increasing Westeberhardia titers in pupae suggest that Westeberhardia provides the host with the tyrosine-precursor 4-hydroxyphenylpyruvate, which may be important for cuticle buildup during development. Thus, Westeberhardia putatively provides novel traits to the host, thereby facilitating adaptation of C. obscurior to novel, arboreal and nutrient-poor habitats. The detection of a Westeberhardia-free host population will allow for elucidating the symbiosis further in the future. The study presented in Chapter 3 introduces the concept of co-option to explain the mechanistic basis of polyphenism in social insects. We show that doublesex and other sex-specifically expressed genes are co-opted into female caste and male morph differentiation of C. obscurior. We hypothesize that this principle is a general patternof caste-differentiation in eusocial insects and thus of one of the major transitions in evolution. Chapter 4 addresses homologous recombination in C. obscurior. Recombination of existing loci is able to generate new genotypes and thus new selectable phenotypes much more rapidly than mutations, due to Hill-Robertson-Interference. During this study it became clear that the interaction between homologous recombination and transposable elements could have led to chromosomal rearrangements within the two studied C. obscurior populations. While rekombination is impeded in regions with high abundance of TEs, regions of high local recombination rates show high levels of genetic divergence between the Brazilian and the Japanese C. obscurior population. Thus recombination is an important player in shaping the C. obscurior genome and likely drives divergence between the two C. obscurior populations. In Chapter 5 the analysis of the C. obscurior holobiont is pursued and discussed in detail. In addition to Westeberhardia, the host C. obscurior also harbors Wolbachia. An overview of the current knowledge about Wolbachia in C. obscurior is given, the potential for possible symbiont-symbiont interaction in the host is discussed und the importance of C. obscurior endosymbionts in the study of the host species is pointed out. Furthermore, an overview of C. obscurior sex determination and the evolution of sex determination systems is given, with a special emphasis on social insects and C. obscurior. Lastly, the evolutionary significance of recombination in this species is discussed in the light of recent findings of supergenes (linked loci with low recombination) in other species. Finally, an outlook on future research on C. obscurior is provided., Eine wichtige Fragestellung der Evolutionsbiologie ist es, ob evolutionäre Neuerungen durch die Entstehung neuer Gene oder durch die Ko-option (Wiederverwendung) von existierenden Genen und Genkaskaden realisiert werden. Diese Arbeit stellt die Bedeutung beider Mechanismen anhand der Ameise C. obscurior dar. Einerseits bietet Endosymbiose mit Bakterien Potential für die Entstehung neuer Gene und Merkmale im Rahmen des Konzept des "Holobionten", während andererseits das Potential für Neuerungen durch die Kooption von existierenden Genen und durch die Durchmischung des Genoms durch homologe Rekombination aufgezeigt wird. Kapitel 1 gibt einen Überblick über den aktuellen Forschungsstand über evolutionäre Neuerungen. Das Kapitel stellt das "Holobiont"-Konzept vor und erklärt das Potential von endosymbiotischen Bakterien für die Evolution des Wirtes. Weiterhin wird ein Überblick über verschiedene Geschlechtsbestimmungssysteme in Insekten gegeben und das Gen doublesex vorgestellt, welches in Kapitel 3 im Detail analysiert wird. Darüber hinaus wird meiotische Rekomination und das Prinzip der Genkartierung beschrieben, welches in Kapitel 4 behandelt und angewandt wird. Die Einleitung endet mit einer Einführung in den Modelorganismus Cardiocondyla obscurior und die ergatoide Männchen Morphe, eine evolutionäre Neuerung in der Gattung Cardiocondyla. In Kapitel 2 wird ein neu entdecktes, endosymbiotisches Bakterium ("Candidatus Westeberhardia cardiocondylae") und dessen Symbiose mit dem Wirt C. obscurior beschrieben. Das starke reduzierte Genom von Westeberhardia und die Lokalisierung des Symbionten in sog. "Bakteriomen" während der Puppenphase sprechen für eine mutualistische Assoziation mit dem Wirt. Die Analyse der Stoffwechselwege des reduzierten Westeberhardia Genoms und ein Anstieg der Bakteriendichte während der Puppenphase deuten darauf hin, dassWesteberhardia den Wirt mit der Tyrosin Vorstufe 4-Hydroxyphenylpyruvat versorgen könnte, das für den Aufbau der Kutikula während der Puppenphase wichtig sein könnnte. Folglich, könnte Westeberhardia es dem Wirt ermöglichen, neue Merkmale zu evolvieren und sich an neue, nährstoffarme Habitate anzupassen. Die Entdeckung einer Westeberhardia-freien Wirtspopulation bietet ideale Voraussetzungen um in Zukunft die Symbiose zwischen C. obscurior und Westeberhardia genauer zu untersuchen. Die in Kapitel 3 präsentierte Studie führt das Konzept der "Kooption" zur Erklärung der Mechanismen bei der Entstehung von Polyphenismen bei sozialen Insekten ein. Die Studie zeigt, dass das Gen doublesex neben anderen geschlechtsspezifisch exprimierten Genen kooptiert wurde, um in C. obscurior die Kastendifferenzierung bei Weibchen und die Morphendifferenzierung der Männchen zu regulieren. Vermutlich könnte dieses Prinzip der Kooption ein genereller Mechanismus bei der Entstehung von Kasten bei sozialen Insekten sein, und damit an einer der wichtigsten evolutionären Neuerungen beteiligt sein. Kapitel 4 behandelt homologe Rekombination in C. obscurior. Durch die "Hill-Robertson-Interferenz" ermöglicht es Rekombination von existierendem genetischen Material viel schneller neue Genotypen und folglich neue selektierbare Phänotpyen zu generieren als zufällige Mutuationen. Während dieser Arbeit zeigte sich eine Interaktion von homologer Rekombination mit transposablen Elementen (TE). Diese Interaktion könnte zu chromosomalen Umlagerungen zwischen zwei C. obscurior Populationen aus Brasilien und Japan geführt haben. Während Rekombination in Regionen mit hohem TE Gehalt niedrig ist, findet sich in Regionen hoher Rekombination eine erhöhte genetische Divergenz zwischen den beiden C. obscurior Populationen aus Brasilien und Japan. Damit ist Rekombination ein wichtiger Faktor in der Genom-Evolution von C. obscurior. In Kapitel 5 wird die Analyse des C. obscurior Holobionten fortgesetzt und im Detail diskutiert. Zusätzlich zu Westeberhardia findet sich im Wirt C. obscurior das Bakterium Wolbachia. Nachdem ein Überblick über Wolbachia in C. obscurior gegeben wurde, wird das Potential für Interaktionen zwischen den beiden Symbionten in der Ameise diskutiert und die Bedeutung der Endosymbionten für das Studium der Wirts-Art herausgearbeitet. Weiterhin wird die Geschlechtsbestimmung in C. obscurior diskutiert, wobei die evolutionären Faktoren welche die Geschlechtsbestimmung von C. obscurior beeinflusst haben könnten, hervorgehoben werden. Schließlich wird die Bedeutung von Rekombination im Hinblick auf die Beschreibung von sog. "Supergenen" in anderen Arten diskutiert. Abschließend wird ein Ausblick auf die zukünftige Forschung am Modelorganismus C. obscurior gegeben.

A hallmark of Alzheimer's disease (AD) is the accumulation of extracellular amyloid-v (Av) plaques in the brains of patients. N-terminally truncated pyroglutamate-modified Av (pEAv) has been described as a major compound of Av species in senile plaques. pEAv is more resistant to degradation, shows higher toxicity and has increased aggregation propensity and v-sheet stabilization compared to non-modified Av. Here we characterized recombinant pEAv(3-40) in aqueous trifluoroethanol (TFE) solution regarding its aggregation propensity and structural changes in comparison to its non-pyroglutamate-modified variant Av(1-40). Secondary structure analysis by circular dichroism spectroscopy suggests that pEAv(3-40) shows an increased tendency to form v-sheet-rich structures in 20% TFE containing solutions where Av(1-40) forms a-helices. Aggregation kinetics of pEAv(3-40) in the presence of 20% TFE monitored by thioflavin-T (ThT) assay showed a typical sigmoidal aggregation in contrast to Av(1-40), which lacks ThT positive structures under the same conditions. Transmission electron microscopy confirms that pEAv(3-40) aggregated to large fibrils and high molecular weight aggregates in spite of the presence of the helix stabilizing co-solvent TFE. High resolution NMR spectroscopy of recombinantly produced and uniformly isotope labeled [U-15N]-pEAv(3-40) in TFE containing solutions indicates that the pyroglutamate formation affects significantly the N-terminal region, which in turn leads to decreased monomer stability and increased aggregation propensity

Syftet med denna studie var att undersöka hur terapeuter inom den offentliga sjukvården resonerar kring svårigheter i att arbeta med trauma. Frågeställningarna var: hur resonerar terapeuter kring svårigheter att arbeta med trauma; vilka känslomässiga reaktioner har de; vad säger de om handledning, kollegialt stöd och organisationen inom vilket de arbetar; samt hur de resonerar kring kultur, språk och tolkanvändning. Semistrukturerade intervjuer genomfördes med fem terapeuter som arbetar inom primärvården respektive psykiatriska öppenvården. Intervjuerna spelades in, transkriberades och analyserades genom Tematisk Analys. Resultaten visar att traumatiserade personer upplevdes som en tung patientgrupp och att de önskade sig mer handledning och utbildning för att klara av arbetet. Det var även svårt för dem att se hur patienterna skickades runt mellan olika vårdinstanser. Resultaten visar också att man upplevde svårigheter kring kulturella skillnader och att arbeta med tolk. Tidsbrist i behandlingarna och underbemanning upplevdes också som försvårande omständigheter i arbetet med trauma. Avslutningsvis diskuteras om den svåra symtomatologin och traumats inbyggda dialektik är bidragande orsaker till att traumatiserade patienter skickas mellan vårdinstanser och upplevs som en tung grupp att arbeta med. Också terapeuternas beskrivningar av underbemanning och tidsbrist diskuterades utifrån de behandlingsrekommendationer som finns och riskerna om dessa inte följs. The purpose of this study was to investigate how psychotherapists within the Swedish health service perceive difficulties in working with trauma. The research questions were how do therapists perceive difficulties in working with trauma; what are their emotional reactions; what are their views concerning supervision, peer support and the organisation within which they work; what thoughts do the therapists have concerning culture, language and the use of interpreters. Semi structured interviews were conducted with five psychotherapists who work in municipal health centers and psychiatric outpatient clinics. The interviews were recorded, transcribed and analysed using thematic analyses. The results show that in general the therapists experienced traumatised people as a difficult group of patients and they felt a need for increased levels of supervision and training. They also experienced difficulties arising from the fact that patients were often moved frequently between different health services. The results also showed that they experienced difficulties due to cultural differences and working with interpreters. Limits on treatment duration and under staffing also contributed to difficulties. The relationships between symptoms and the dialectics of trauma and the fact that patient group are often passed between health services and experienced as a difficult were discussed.

Adaptation requires genetic variation, but founder populations are generally genetically depleted. Here we sequence two populations of an inbred ant that diverge in phenotype to determine how variability is generated. Cardiocondyla obscurior has the smallest of the sequenced ant genomes and its structure suggests a fundamental role of transposable elements (TEs) in adaptive evolution. Accumulations of TEs (TE islands) comprising 7.18% of the genome evolve faster than other regions with regard to single-nucleotide variants, gene/exon duplications and deletions and gene homology. A non-random distribution of gene families, larvae/adult specific gene expression and signs of differential methylation in TE islands indicate intragenomic differences in regulation, evolutionary rates and coalescent effective population size. Our study reveals a tripartite interplay between TEs, life history and adaptation in an invasive species., Genetic variation is key to species evolution. Here the authors sequence two phenotypically distinct populations of the ant Cardiocondyla obscurior, and find accumulations of transposable elements correlating with genetic variation that may have a role in differentiation, adaptation and speciation.

Alzheimer's disease (AD) is the most prominent neurodegenerative disease affecting more than 24 million people worldwide. Currently, it is the sixth-leading cause of death, but until now there is no causal therapy available. The amyloid-beta (Aβ) peptide plays an important role in the pathology of the disease. Especially the soluble, most harmful neurotoxic oligomers of Aβ are discussed to be responsible for the development and progression of the disease. In our group we identified the D-enantiomeric peptide D3 via mirror image phage display, which reduces the formation of Aβ oligomers in vitro [1-3].

Alzheimer's disease (AD) is the most prominent type of dementia in elderly people. Until now there is no curative therapy available.Amyloid beta (Aβ) is assumed to play a major role in the development and progression of the disease. Freely diffusible, toxic Aβ oligomers seem to have a major toxicological impact.