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Although many plants are dispersed by wind and seeds can travel long distances across unsuitable matrix areas, a large proportion relies on co-evolved zoochorous seed dispersal to connect populations in isolated habitat islands. Particularly in agricultural landscapes, where remaining habitat patches are often very small and highly isolated, mobile linkers as zoochorous seed dispersers are critical for the population dynamics of numerous plant species. However, knowledge about the quali- or quantification of such mobile link processes, especially in agricultural landscapes, is still limited. In a controlled feeding experiment, we recorded the seed intake and germination success after complete digestion by the European brown hare (Lepus europaeus) and explored its mobile link potential as an endozoochoric seed disperser. Utilizing a suite of common, rare, and potentially invasive plant species, we disentangled the effects of seed morphological traits on germination success while controlling for phylogenetic relatedness. Further, we measured the landscape connectivity via hares in two contrasting agricultural landscapes (simple: few natural and semi-natural structures, large fields; complex: high amount of natural and semi-natural structures, small fields) using GPS-based movement data. With 34,710 seeds of 44 plant species fed, one of 200 seeds (0.51%) with seedlings of 33 species germinated from feces. Germination after complete digestion was positively related to denser seeds with comparatively small surface area and a relatively slender and elongated shape, suggesting that, for hares, the most critical seed characteristics for successful endozoochorous seed dispersal minimize exposure of the seed to the stomach and the associated digestive system. Furthermore, we could show that a hare's retention time is long enough to interconnect different habitats, especially grasslands and fields. Thus, besides other seed dispersal mechanisms, this most likely allows hares to act as effective mobile linkers contributing to ecosystem stability in times of agricultural intensification, not only in complex but also in simple landscapes.

Agricultural land-use practices have intensified over the last decades, leading to population declines of various farmland species, including the European hare (Lepus europaeus). In many European countries, arable fields dominate agricultural landscapes. Compared to pastures, arable land is highly variable, resulting in a large spatial variation of food and cover for wildlife over the course of the year, which potentially affects habitat selection by hares. Here, we investigated within-home-range habitat selection by hares in arable areas in Denmark and Germany to identify habitat requirements for their conservation. We hypothesized that hare habitat selection would depend on local habitat structure, that is, vegetation height, but also on agricultural field size, vegetation type, and proximity to field edges. Active hares generally selected for short vegetation (1-25 cm) and avoided higher vegetation and bare ground, especially when fields were comparatively larger. Vegetation >50 cm potentially restricts hares from entering parts of their home range and does not provide good forage, the latter also being the case on bare ground. The vegetation type was important for habitat selection by inactive hares, with fabaceae, fallow, and maize being selected for, potentially providing both cover and forage. Our results indicate that patches of shorter vegetation could improve the forage quality and habitat accessibility for hares, especially in areas with large monocultures. Thus, policymakers should aim to increase areas with short vegetation throughout the year. Further, permanent set-asides, like fallow and wildflower areas, would provide year-round cover for inactive hares. Finally, the reduction in field sizes would increase the density of field margins, and farming different crop types within small areas could improve the habitat for hares and other farmland species.

Species demanding specific habitat requirements suffer, particularly under environmental changes. The smallest owl of Africa, the Sokoke Scops Owl (Otus ireneae), occurs exclusively in East African coastal forests. To understand the movement behaviour and habitat demands of O. ireneae, we combined data from radio-tracking and remote sensing to calculate Species Distribution Models across the Arabuko Sokoke forest in southern Kenya. Based on these data, we estimated the local population size and projected the distribution of current suitable habitats. We found that the species occurs only in Cynometra woodland with large old trees and dense vegetation. Based on home range sizes and the distribution of suitable forest habitats, the local population size was estimated at

Die Reaktionen homoatomare [E9]x--Zintl-Cluster (E = Ge, Sn; x = 2, 3, 4) sowie homoatomare Cluster mit funktionellen Gruppen wurden mit niedervalenten Organylen der Gruppe 13 und 14 mit dem Ziel umgesetzt, Clustererweiterung vorzunehmen. Die Reaktion von K4Ge9 mit GaCp* lieferte das Anion [Ge9Ga-GaGe9]4-, in welchem die Ge9-Cluster mit einem Galliumatomtom erweitert sind. Zudem sind zwei Cluster über eine [Ga-Ga]-Bindung verknüpft. Reaktionen mit niedervalenten Siliciumverbindungen führten dagegen Abspaltung des organischen Restes am Silicium, wie die Bildung der Verbindungen [K(dipp)2][Ge9(Si(SiMe3)3)3]·tol und [dipp-H][Ge9(Si(SiMe3)3)3]·2acn zeigt. Die Verbindungen wurden mittels Röntgenbeugung an Einkristallen und NMR-Spektroskopie charakterisiert. Der Einsatz eines im Verlauf der Disseration aufgebauten ESI-MS erlaubte es, die Spezies in Lösung durch ihre charakteristische Isotopenverteilung massenspektrometrisch zu charakterisieren. The reactions of homoatomic [E9]x- Zintl clusters (E = Ge, Sn; x = 2, 3, 4) as well as homoatomic clusters with functional groups were implemented with low valent organyls of group 13 and 14 with the aim of expanding the cluster. The reaction of K4Ge9 with GaCp * yielded the anion [Ge9Ga-GaGe9]4-, in which the Ge9 clusters are expanded with a gallium atom. In addition, two clusters are linked by a [Ga-Ga] bond. Reactions with low-valent silicon compounds, on the other hand, lead to the splitting off of the organic residue on silicon, such as the formation of the compounds [K(dipp)2][Ge9(Si(SiMe3)3)3]·tol and [dipp-H][Ge9(Si(SiMe3)3)3]·2acn shows. The compounds were characterized by X-ray diffraction on single crystals and NMR spectroscopy. The use of an ESI-MS set up in the course of the dissertation made it possible to characterize the species in solution by means of their characteristic isotope distribution by mass spectrometry.

Im Rahmen einer Interventionsstudie wird die Entwicklung retinaler Gefäßparameter von 282 Schulkindern im Hinblick auf Zusammenhänge mit anthropometrischen Parametern, kardiometabolischen Risikofaktoren, hsCRP sowie Aktivität bzw. Inaktivität untersucht. Nach 4 Jahren waren die retinalen Arteriolen der Interventionsgruppenmitglieder enger als die der Kontrollgruppe, die retinalen Venolendurchmesser nahmen in beiden Gruppen ab. Eine ungünstige Entwicklung retinaler Gefäßparameter stand im Zusammenhang mit kardiometabolischen Risikofaktoren und einem Anstieg der Sitzzeit. This thesis describes the development of retinal vessel diameters of 282 children as part of a school-based interventional study with respect to anthropometric data, cardiometabolic risk factors, hsCRP, and physical activity or inactivity, respectively. After 4 years, members of intervention group showed tighter retinal arterioles than members of control group; retinal venular diameters declined in both groups. Unfavorable progression of retinal vessel diameters was found to be associated with cardiometabolic risks and an increasing sedative activity.

Kurzzusammenfassung 1. Hintergrund und Ziele Ziel der vorliegenden Arbeit ist es, einen Überblick über neurophysiologische Auswirkungen des Krankheitsbildes „obstruktive Schlafapnoe“ (OSA) zu geben sowie darüber hinaus deren Pathogenese und klinische Manifestationen darzustellen. Die verwendeten Studien werden bezüglich ihrer Evidenz bewertet, um ein umfassendes Bild der potenziellen Folgen zu erhalten, die diese schlafbezogene Atmungsstörung auf Struktur, Aktivität und Metabolismus des Gehirns der betroffenen Patienten hat. 2. Methoden Die Suche nach Publikationen, wissenschaftlichen Artikeln und Büchern zur Thematik erfolgte überwiegend mittels elektronischer Datenbankrecherche. In Anlehnung an die Empfehlungen des Cochrane Instituts zur Literaturbewertung sowie anhand eines selbst erstellten Bewertungssystems wurden Meta-Analysen, Querschnittsstudien, Fall-Kontroll-Studien, Kohortenstudien sowie tierexperimentelle Studien ausgewählt und kritisch bewertet. Unter Berücksichtigung der entsprechenden Studienqualitäten konnten dann allgemeine Schlussfolgerungen gezogen werden. 3. Ergebnisse und Beobachtungen Da die Studienlage zur vorliegenden Thematik sehr umfangreich ist, sollen in dieser Kurzzusammenfassung nur die wesentlichen Aspekte genannt werden. Zerebrale Anomalitäten sowie neurophysiologische Defizite bei OSA-Patienten entstehen primär durch die pathologischen Bedingungen intermittierende Hypoxie und Schlaffragmentierung. Beide Faktoren führen über molekulare und zelluläre Signalwege zu anatomisch-strukturellen, funktionellen, biochemisch-metabolischen und elektrokortikalen Veränderungen im Gehirn der Betroffenen. Gemessen werden konnten etwa, um einige Beispiele zu nennen, Volumenveränderungen bestimmter Hirnareale, lokal veränderte Metabolitkonzentrationen, anomale Aktivierung und Vernetzung bestimmter Hirnregionen sowie Abweichungen im EEG-Rhythmus und der Schlafarchitektur. Neben dem Hauptsymptom der extremen Tagesschläfrigkeit lassen sich eine Reihe weiterer klinischer Dysfunktionen und Krankheitsbilder auf die gemessenen Abweichungen zurückführen. So gibt es Assoziationen mit Störungen der Sinneswahrnehmung, mit neurologischen Entitäten wie Alzheimer, Parkinson, Epilepsie, Kopfschmerzen oder Depressionen sowie mit der Beeinträchtigung kognitiver Funktionen. 4. Schlussfolgerungen Zusammenfassend ist festzuhalten, dass das Krankheitsbild OSA weitreichende Auswirkungen variabler Tragweite auf die Neurophysiologie der Betroffenen haben kann. Um der Entstehung irreversibler neurologischer Schäden und kognitiver Defizite bei OSA-Patienten vorzubeugen bzw. deren Ausmaß abzuschwächen, ist daher eine frühzeitige Eliminierung der pathologischen Bedingungen intermittierende Hypoxie und Schlaffragmentierung mittels adäquater Therapie von essenzieller Bedeutung. Summary 1. Background and objectives The aim of this work is to give an overview of the neurophysiological effects of obstructive sleep apnea (OSA) and furthermore to present its pathogenesis and clinical manifestations. The studies used will be evaluated on their level of evidence in order to obtain a comprehensive picture of the potential consequences of this sleep-related breathing disorder on structure, activity and metabolism of the affected patients’ brains. 2. Methods The search for publications, scientific articles and books on the subject was carried out predominantly by means of electronic database research. Based on the recommendations of the Cochrane Institute on literature evaluation and on a self-developed evaluation system, meta-analyses, cross-sectional studies, case-control studies, cohort studies and animal studies were selected and critically evaluated. Considering the relevant study qualities, general conclusions could then be drawn. 3. Results and observations Since the study situation on the subject is very extensive, only the essential aspects shall be mentioned in this short summary. Cerebral abnormalities and neurophysiological deficits in OSA patients are primarily caused by the pathological conditions of intermittent hypoxia and sleep fragmentation. Both factors lead via molecular and cellular signalling pathways to anatomical-structural, functional, biochemical-metabolic and electrocortical changes in the brain of those affected. To name a few examples, volume changes of certain brain areas, locally altered metabolite concentrations, abnormal activation and networking of certain brain regions as well as deviations in EEG rhythm and sleep architecture could be measured. In addition to the main symptom of excessive daytime sleepiness, a number of other clinical pictures and dysfunctions can be attributed to the measured deviations. There are associations with disorders of sensory perception, with neurological entities such as Alzheimer's, Parkinson's, epilepsy, headaches or depression as well as with impairment of cognitive functions. 4. Conclusions In summary, it can be stated that the clinical picture of OSA can have far-reaching effects of variable magnitude on the neurophysiology of those affected. In order to prevent the development of irreversible neurological damage and cognitive deficits in OSA patients or to reduce their extent, early elimination of the pathological conditions of intermittent hypoxia and sleep fragmentation by adequate therapy is of essential importance.

Multivalente Peptid-Polymerkonjugate bieten ein bislang weitgehend ungenutztes Potential als Inhibitoren für Protein-Protein Interaktionen. Hierbei sind insbesondere ihre proteolytische Beständigkeit und die mögliche Zellpermeabilität von Interesse. Des Weiteren können durch eine multivalente Präsentation Affinitätssteigerung gegenüber ihren Zielstrukturen im Vergleich zu ihren monovalenten Pendants erreicht werden. Somit könnten potentiell potente Inhibitoren entwickelt werden. In der vorliegenden Arbeit wurden Dextrankonjugate als multivalente, zellgängige Inhibitoren der Tandem-WW-Domäne des pre-mRNA Splicingproteins FBP21 und der West-Nil-Virus Protease NS2B-NS3 eingesetzt. Hierbei sollte besonders die funktionelle Untersuchung der multivalenten Inhibitoren in vitro und in vivo im Fokus dieser Arbeit stehen. Als inhibitorische Funktionspeptide dienten zwei Prolin-reiche Sequenzen, das affine Peptid WPPPPRVPR (W) und die hochaffine Sequenz WPPPPRVPRWPPPPRVPR (W2), die bereits als monovalente Peptide eine gute Bindungsaffinität zum FBP21 aufwiesen. Die Beladung der synthetisierten Konjugate konnten mittels eigens entwickelter Analysemethodik in einer Kombination aus NMR- und Absorptionsspektroskopie bestimmt werden. Die so ermittelten Molmassen ließen sich mittels Gelpermeationschromatographie verifizieren. Weiterführend wurden die Bindungsaffinitäten der Konjugate zum FBP21 anhand isother-maler Titrationskalorimetrie ermittelt. Hierbei zeigten Konjugate, die das hochaffine Peptid trugen im Vergleich mit der affinen W-Sequenz eine stärkere Bindungsaffinität bei geringerer Beladungszahl. Somit wurden die hochaffinen W2-Konjugate für die weiteren biochemischen Untersuchungen eingesetzt. Da das FBP21 im Zellnukleus lokalisiert ist, sollte die nukleare Aufnahme der Konjugate induziert werden, um eine Inhibition des FBP21 bewirken zu können. Hierfür wurde eine Kombination aus zellpenetrierendem Peptid und Kernlokalisationssequenz untersucht. Die endosomale Freisetzung der Konjugate in das Zytosol und anschließende Aufnahme in den Zellkern wurde durch die gewählte Kombination der zellpenetrierenden Peptide in Verbindung mit dem hochaffinen Funktionspeptid erreicht. Hierbei war jedoch die Bela-dung der Dextrane mit den jeweiligen Peptidspezies nicht beliebig wählbar, da bei hohen Beladungszahlen eine Zytotoxizität der Konstrukte, hervorgerufen durch die biologische Aktivität des Inhibitors, auftrat. Nachdem die Zellaufnahme bestätigt werden konnte, wurde die Splicingaktivität der hochaffinen Peptid-Dextrankonjugate anhand eines in vitro Splicing-Assays bestimmt. Die multivalente Präsentation der Funktionspeptide schien hierbei ausschlaggebend für den inhibitorischen Effekt der Konjugate zu sein. Abschließend sollte anhand eines Pull-down-Assays die Interaktion der Konjugate mit dem FBP21 bestätigt und potentielle weitere Interaktionspartner ausfindig gemacht werden. Es konnte hierbei eine deutliche Interaktion des Funktionspeptid-tragenden Konjugats mit dem FBP21 gegenüber der Negativkontrolle gesehen werden. Weiterhin wurde auch die Interaktion einer Vielzahl an weiteren Proteinen mit den Konjugaten detektiert, welche zu einem großen Anteil aus dem Splicingzyklus oder nahverwandten Prozessen wie der Transkription stammen. Somit sind die verwendeten Peptid-Dextrankonjugate als PPI-Inhibitoren für das pre-mRNA Splicing einsetzbar. Für die Entwicklung zellgängiger, flaviviraler Inhibitoren wurden Dextrankonjugate syn-thetisiert, die das potente, literaturbekannte Peptidomimetikum Phenacyl-Lys-Lys-GCMA verwendeten. Das Peptidomimetikum wies hierbei selbst nur bei erhöhten Konzentration eine Zellpermeabilität auf. Um eine Zellgängigkeit der Konjugate zu gewährleisten, wurden somit zusätzlich zellpenetrierende Peptide (TAT) an die Dextrane gekuppelt. Bei Untersuchung der Aktivitäten der Inhibitoren zeigte sich, dass die TAT-tragenden Konjugate generell eine bessere Aktivität gegenüber den Flaviviren West-Nil-, Dengue- und Zika-Virus in vitro und in vivo aufwiesen als Konjugate, die nur das Peptidomimetikum trugen. Dieses ist dadurch begründet, dass das TAT-Peptid selbst als Substrat für die NS2B-NS3 Protease wirken kann und somit diese inhibiert. Die Verwendung der Peptidomimetika in Kombination mit dem TAT zeigte hierbei einen multivalenten Effekt der Inhibition., Multivalent peptide-polymer conjugates offer a largely untapped potential as inhibitors of protein-protein interactions. Especially their stability towards proteolysis and a potential of increased cell permeability are of interest. Furthermore, they exhibit strongly increased binding affinities towards their target structures in comparison to their monovalent entities. Thus, more potent inhibitors could be obtained. In the following work, dextran conjugates have been used as multivalent, cell-penetrating inhibitors for the tandem-WW-domains of the pre-mRNA splicing protein FBP21 and the West Nile virus protease NS2B-NS3. In this context, the dextran conjugates were investigated in depth on their functional properties in in vitro and in vivo experiments. Two proline-rich sequences, the peptide WPPPPRVPR (W) and the high-affinity sequence WPPPPRVPRWPPPPRVPR (W2), were used as inhibitory peptides due to their good binding activities towards FBP21 as monovalent peptides. The loading of the synthesized conjugates could be determined using a specially developed analysis methodology, which combined the use of NMR and absorp-tion spectroscopy. Calculated molecular masses could be confirmed using gel permeation chromatography. Afterwards, the binding affinities of the conjugates were determined with isothermal titration calorimetry. Conjugates bearing the high-affinity W2-peptide showed a higher binding affinity at a lower peptide loading on the dextran than the W-sequence. Consequently, the W2-conjugates were used for the following biochemical investigations. Since FBP21 is localized in the cell nucleus, the nuclear uptake of the conjugates needed to be induced to enable the inhibition of FBP21. Therefore, a combination of a cell-pene-trating peptide and a nuclear localization sequence were investigated. The endosomal release of the conjugates into the cytosol and following uptake into the cell nucleus was successful for a combination of the cell-penetrating peptide system and the functional W2-peptide. Due to high cytotoxicity at high peptide loading, the number of peptides coupled to the dextrans was not freely selectable and has to be taken into consideration. This cytotoxicity was most likely due to the biological activity of the inhibitors and therefore indicated a good potency for the system. After confirmation of the cellular uptake, the splicing activity of the W2-conjugates were investigated using an in vitro splicing assay. The multivalent presentation of the functional peptides seemed to be crucial for the inhibitory effect of the conjugates. Finally, the interaction of the conjugates with FBP21 and the possible interaction with other proteins was investigated with a pulldown assay. The interaction of the W2-bearing conjugate with FBP21 could be seen clearly in comparison with the negative control. Furthermore, a mul-titude of other peptides from the cell lysate bound to the conjugate. Most of the bound proteins were splicing proteins or interaction partners from closely related processes (e.g. transcription). Therefore, the synthesized conjugates can be used as PPI-inhibitors of pre-mRNA splicing. Additionally, dextran conjugates were synthesized as cell-permeable, flavivirale inhibitors. In this case the potent peptidomimetic Phenacyl-Lys-Lys-GCMA was used as the inhibitory component. The peptidomimetic itself only showed cellular uptake at high concentrations. Therefore, to insure cellular uptake of the conjugates, the cell-penetrating peptide TAT was additionally coupled onto the dextran backbone. For activity investigations of the synthesized inhibitors the TAT-bearing conjugates generally showed a higher activity in vitro and in vivo towards the flaviviruses West-Nile, Dengue and Zika compared to purely peptidomimetic conjugates. This enhanced activity is due to the fact that TAT itself can act as a substrate for the NS2B-NS3 protease and therefore inhibit the virus. A combination of both peptidomimetic and TAT leads to an increase cooperative effect of the inhibition.

Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. The Lancet Publishing Group

Summary Post‐dispersal seed predation and endozoochorous seed dispersal are two antagonistic processes in relation to plant recruitment, but rely on similar preconditions such as feeding behavior of seed consumers and seed traits. In agricultural landscapes, rodents are considered important seed predators, thereby potentially providing regulating ecosystem services in terms of biological weed control. However, their potential to disperse seeds endozoochorously is largely unknown. We exposed seeds of arable plant species with different seed traits (seed weight, nutrient content) and different Red List status in an experimental rye field and assessed seed removal by rodents. In a complementary laboratory experiment, consumption rates, feeding preferences, and potential endozoochory by two vole species (Microtus arvalis and Myodes glareolus) were tested. Seed consumption by rodents after 24 h was 35% in the field and 90% in the laboratory. Both vole species preferred nutrient‐rich over nutrient‐poor seeds and M. glareolus further preferred light over heavy seeds and seeds of common over those of endangered plants. Endozoochory by voles could be neglected for all tested plant species as no seeds germinated, and only few intact seeds could be retrieved from feces. Synthesis and applications. Our results suggest that voles can provide regulating services in agricultural landscapes by depleting the seed shadow of weeds, rather than facilitating plant recruitment by endozoochory. In the laboratory, endangered arable plants were less preferred by voles than noxious weeds, and thus, our results provide implications for seed choice in restoration approaches. However, other factors such as seed and predator densities need to be taken into account to reliably predict the impact of rodents on the seed fate of arable plants.

Riparian thickets of East Africa harbor a large number of endemic animal and plant species, but also provide important ecosystem services for the human being settling along streams. This creates a conflicting situation between nature conservation and land‐use activities. Today, most of this former pristine vegetation is highly degraded and became replaced by the invasive exotic Lantana camara shrub species. In this study, we analyze the movement behavior and habitat use of a diverse range of riparian bird species and model the habitat availability of each of these species. We selected the following four riparian bird species: Bare‐eyed Thrush Turdus tephronotus, Rufous Chatterer Turdoides rubiginosus, Zanzibar Sombre Greenbul Andropadus importunus insularis, and the Kenyan endemic Hinde′s Babbler Turdoides hindei. We collected telemetric data of 14 individuals during a 2 months radio‐tracking campaign along the Nzeeu River in southeast Kenya. We found that (1) all four species had similar home‐range sizes, all geographically restricted and nearby the river; (2) all species mainly use dense thicket, in particular the invasive L. camara; (3) human settlements were avoided by the bird individuals observed; (4) the birds' movement, indicating foraging behavior, was comparatively slow within thickets, but significantly faster over open, agricultural areas; and (5) habitat suitability models underline the relevance of L. camara as suitable surrogate habitat for all understoreyed bird species, but also show that the clearance of thickets has led to a vanishing of large and interconnected thickets and thus might have negative effects on the population viability in the long run.