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Die Rolle von Ceramiden und assoziierten Faktoren in der Bildung von Coronavirus-induzierten replikativen Organellen
(2025) Salisch, Florian
RNA viruses have evolved diverse strategies to re-program and exploit host cellular functions and molecules, including cellular lipids, to ensure efficient virus replication and production of infectious virus progeny. A conserved feature of plus-strand RNA virus replication is the formation of membranous microenvironments (replicative organelles, ROs) in virus-infected cells. RO formation is known to be initiated by virus-encoded membrane-associated nonstructural proteins and involves extensive remodeling of host cell membranes. This process is thought to involve cellular enzymes responsible for synthesizing and modifying specific lipids. In this study, I investigated the potential roles of specific cellular sphingolipids and enzymes acting on sphingolipids in the replication of different coronaviruses. The data revealed that, following infection, cellular ceramide species increase significantly, whereas sphingomyelin levels decreased, indicating an involvement of sphingomyelinases that convert sphingomyelin to ceramide. To verify this, I targeted the cellular sphingomyelinases using pharmacological and genetic approaches. I could provide evidence that neutral sphingomyelinase 2 (nSMase2) plays an essential role in an early phase (but not entry) of coronavirus replication in Huh-7-ACE2 cells. Furthermore, I was able to demonstrate a colocalization of neutral sphingomyelinase 2 and ceramide, but not sphingomyelin, with both infection-induced and genetically induced ROs. Ceramides and coronaviral ROs were found to colocalize in different cell systems used in this study. However, in another set of experiments, I also obtained data to suggest that the extent of specific sphingolipid deregulations and the role of nSMase2 in coronavirus infections may vary among different infection systems, depending on the cell type used. Taken together, this study strongly suggests that ceramides serve as crucial lipid building blocks in the formation of coronaviral ROs in different cell types, suggesting that inhibition of cellular ceramide production may represent a potential antiviral strategy against coronavirus infections. However, the mechanisms of ceramide generation or recruitment to specific intracellular sites seem to vary depending on the cell type used and, possibly, the baseline ceramide levels in these cell types. Further investigation is required to clarify these variations and their biological implications.
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Die sprachlich-diskursive Legitimation von Militäreinsätzen. Eine diskurslinguistische Analyse französischer Parlamentsdebatten zur Opération Serval (Mali)
(2025) Sommer, Luana
Die Dissertation leistet einen Beitrag zur Erforschung der sprachlich-diskursiven Legitimation von Militäreinsätzen und untersucht anhand eines Korpus französischer Parlamentsdebatten die Legitimierung der "Opération Serval" (Mali). Das im Zuge der Arbeit entwickelte, diskurslinguistische "Modell der Makromechanismen der Legitimation" (MML) eröffnet die Möglichkeit einer systematischen Analyse solcher Legitimationsvorhaben und bildet zugleich eine Grundlage, diese einer fundierten Kritik zu unterziehen.
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Genetic study of Red Maasai sheep and their Dorper crossbred’s performance in sub-Saharan Africa
(2025) Oyieng, Edwin Pancras
The aim of this thesis was to study the performance of the Red Maasai sheep, the Dorper sheep and their crosses reared in a semi-arid environment. The study involved the analysis of reproduction parameters, survival of lambs and ewes length of productive life, the impact of heat stress on growth, and developed novel resilience phenotypes for the sheep population. The main breed groups in the breeding program comprised pure Dorper (DDDD), pure Red Maasai (RRRR), 75%Dorper-25%Red Maasai (DDDR) and 50%Dorper-50%Red Maasai – F1 (DDRR). R and ASReml-R software were used to evaluate reproduction parameters. Survival of lambs and the length of productive life of ewes were analysed using Cox and Weibull hazard models of the Survival Kit Version 6.12 software. Random regression models fitted with reaction norm functions were used to assess the impact of heat stress on growth and derive novel resilience phenotypes for growth in response to different levels of heat stress. Information generated through studying the reproductive performance of the flock is presented in Chapter 2. The pure Red Maasai sheep had significantly lower values for average age at first lambing (AFL), ewe birth weight (EBWT), ewe weaning weight (EWWT), litter birth weight (LBWT) and litter weaning weight (LWWT) compared to other breeds studied. The birth type (single or twins), sex of the lamb and parity in which the lambs were born significantly affected ewes’ birth and weaning weights. The overall heritability estimates of AFL (0.09±0.04) and LI (0.00±0.01) were not significant (P>0.05) while the heritability estimates for EBWT (0.38±0.04), EWWT (0.23±0.03), LBWT (0.19±0.03) and LWWT (0.09±0.02) were significant (P<0.05). The repeatability estimates were low for LBWT (0.25), LWWT (0.16) and that of lambing interval (LI) was near zero. Genetic and phenotypic correlations showed strong positive relationships between ewe and lamb weights. The Red Maasai had higher genetic and phenotypic correlations and genetic gains for the traits studied compared to the pure Dorper while the DDRR breed combination had a higher genetic gain among the crosses. LI had negative genetic correlations with LBWT and LWWT while AFL had positive genetic correlations with LBWT and LWWT. The phenotypic trends for AFL and LWWT showed a negative association with rainfall index over the years. Chapter 3 presents the results of pre- and post-weaning lamb survival to yearling, and ewes length of productive life. The pure Red Maasai lambs and ewes had better pre-weaning lamb survival rates and better productive life compared to the other breeds. Overall, 95% and 83% of lambs survived to weaning (90 days) and yearling (365 days), respectively. The Red Maasai lambs had the lowest mortality rates (2%) while Dorper lambs had the highest post-weaning mortality (24%) among the breeds. Lamb survival was significantly influenced by the season of birth, parity in which the lambs were born, birth type (single or twin) and birth weight. Single born lambs, those born during the wet season, offspring of multiparous ewes, and those having higher birth weights (>3kg) were associated with lower mortality risks. Ewe longevity was significantly affected by the breed, age at first lambing, parity and birth weight. Ewes of DDDR breed combination and those that had heavier birth weights (>3Kgs) had the highest risk of being culled, while ewes with a higher age at first lambing (>975 days old) and more than one lambing were less likely to be culled. Pre-weaning heritability estimates for survival (0.10–0.14) were higher than post-weaning estimates (0.01-0.05). The Red Maasai had the highest genetic gain for pre-weaning survival (-0.026) compared to DDDR (-0.018), F1 (-0.011), and Dorper (-0.012). General weakness, often due to poor nutrition, posed the highest risk for of lambs dying post-weaning (12.99 risk ratio), followed by diseases like enterotoxemia and sheep pox (6.006 risk ratio). The impact of heat stress on the growth of sheep and novel resilience phenotypes for growth are presented in Chapter 4. Heat stress, expressed as Temperature-Humidity Index (THI), significantly affected the growth of the sheep. The Red Maasai sheep had a higher tolerance for heat stress compared to the other breeds studied. The THI break points, when growth is affected by heat stress, were 78.75, 78.71, 78.42 and 77.93 for RRRR, DDDD, DDRR and DDDR respectively. At the THI break point, the growth rate declined at a rate of 0.06 Kgs, 0.09 Kgs, 0.05 Kgs and 0.15 in live weight gain per unit change in THI for RRRR, DDDD, DDRR and DDDR respectively. Random regression models fitted with reaction norm functions were used to develop two resilience phenotypes namely: Response and Stability. These resilience phenotypes were developed at THI 70 (representing low/no heat stress) and THI 85 (representing high heat stress). The breed, sex, type of birth, dams’ parity and season of birth significantly affected the stability of growth at low and high heat stress. Genetic correlations of resilience phenotypes at THI 85 with pre-weaning live weight gain (LWG1) were antagonistic and significant but not for post-weaning live weight gain (LWG2). Strong positive genetic and phenotypic correlations existed between response and its corresponding stability trait. The heritability estimates of resilience traits ranged from 0.12 for Response at THI 70 to 0.16 for Stability at THI 85. The better lamb survival and ewe longevity, and high tolerance to heat stress of the Red Maasai breed are an indication of their suitability for the harsh environment. Crossbreeding of the Red Maasai with Dorper has the potential to optimize growth and reproductive efficiency in the semi-arid environment. The moderate heritability estimates for resilience phenotypes in the population studied highlight opportunities for selective breeding to enhance resilience for growth under the changing climatic conditions. Context-specific improved animal management practices can increase the survival of lambs, improve their reproductive performance and reduce the impact of heat stress on growth
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Luminescent and Conductive Hybrid Materials based on Nanoscale Metal-Organic Frameworks and (Bio)Polymers
(2025-05) Maxeiner, Moritz
This PhD thesis is centred around a unifying theme: the design and fabrication of hybrid materials that integrate nanoscale metal-organic frameworks (nanoMOFs) with (bio)polymers, targeting advancements in materials science and greener chemistry. A multi-faceted research approach has been applied to address this topic, with three main objectives: first, to synthesise nanoscale versions of bulk MOFs known from the literature; second, to develop nanoMOF@polymer hybrid materials with multi-level anti-counterfeiting mechanisms; and third, to synthesise environmentally friendly nanoMOF@biopolymer materials according to green chemistry principles. During the elaboration of the set scientific scope, all key objectives were successfully achieved, leading to notable achievements in the areas studied. A surfactant-assisted bottom-up synthesis route has successfully produced nanoMOFs with enhanced photophysical and morphological properties compared to their bulk versions. Mixed-matrix-membranes (MMMs) and powders composed of lanthanide-containing nanoMOFs (nLn3+-MOFs) and anthropogenic polymers (APs) have been developed, exhibiting multi-level anti-counterfeiting with interconnected properties, making them highly secure and difficult to replicate, thereby suitable for security-related applications. Aiming towards sustainability, developed nLn3+-MOFs were combined successfully with biopolymers yielding biodegradable and recyclable MMMs, hydrogels and cryogels. These bio-based materials demonstrating high regeneration capacity and stability over multiple recycling steps, align with green chemistry principles. Dispersibility and particle distribution benefit from the nanocharacter of nLn3+-MOF particles, which is a critical requirement for stable and resilient hybrid materials. The visible (Vis= Eu3+, Tb3+) and invisible (NIR= Yb3+) photoluminescence of developed nLn3+-BDC (BDC2−= benzene-1,4-dicarboxylate), together with the conductivity of the APs polystyrene sulfonate (PSS) and pyrolysed resorcinol-formaldehyde (pRF) were used to create an additive multi-level anti-counterfeiting. Each feature (Vis-light, NIRlight, conductivity) represents a certain level of security, while they are interconnected by optical and physical properties – changing one will inevitably change another of the levels. The materials developed are designed to be difficult to replicate for unambiguous marking of valuable goods. As materials science has to address sustainability to overcome environmentally relevant challenges in the future, APs have been replaced by biodegradable nature-based biopolymers agar and gelatine. Luminescent MMMs made from nEu3+-BDC@biopolymers have been successfully recycled ten-times, while the red luminescence allows for the monitoring of the material’s condition. Resilient nEu3+-BDC in boiling water and freezing temperatures as well as water-based synthesis routes, render these materials suitable alternatives for AP-based hybrid materials. Altogether: improved synthesis techniques, application-driven approaches and biodegradable alternatives enable the creation of advanced nanoMOF@(bio)polymer hybrid materials supporting anti-counterfeiting, sustainability and circular economy.
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Entwicklung eines Diagnoseschlüssels für die Innere Medizin des Pferdes anhand einer retrospektiven Studie von 13.550 Fällen aus den Jahren 2000 - 2020
(2024) Klinkel, Samira
Eine retrospektive Auswertung von Patientendaten der Klinik für Pferde, Innere Medizin (PFI), der Justus-Liebig-Universität Gießen bildete die Grundlage für das Hauptziel dieses Dissertationsprojektes, die Entwicklung eines speziesspezifischen Diagnoseschlüssels für internistische Diagnosen bei Pferden. Die Daten umfassten alle Pferde, Ponys und Esel, die von 2000 bis 2020 in der PFI ambulant oder stationär behandelt wurden. Der Hauptzielparameter bestand in der individuellen Hauptdiagnose, die anhand eines ersten Diagnosekatalogs eingeteilt und verschlüsselt wurde. Dieser erste Diagnoseschlüssel enthielt 14 Hauptgruppen, meist basierend auf Organsystemen. Jede Hauptgruppe war in maximal vier Stufen unterteilt, um die Diagnosen zu hierarchisieren. Pro Fall wurde eine Haupt- und bis zu zwei Nebendiagnosen, Outcomes und patientenbezogene Angaben wie Alter, Geschlecht, Rasse, Dauer des Aufenthalts, Erkrankungsdauer und eventuelle Wiedervorstellungen in eine Exceltabelle überführt. Über 21 Jahre (Januar 2000 bis Dezember 2020) wurden die Daten von 14.034 Patienten der PFI erfasst. Es wurden 484 Begleitpferde ausgeschlossen, was zu 13.550 Hauptdiagnosen führte. Die jährliche Patientenanzahl variierte zwischen 497 (2000) und 822 (2019), mit einem Median von 626. Das Durchschnittsalter der Patienten stieg von 9,9 (2000) auf 13,7 Jahre (2020), was eine hoch signifikante Zunahme (p < 0,0001) um ca. 2 Monate pro Jahr ergab. Die Verteilung des Geschlechts zeigte leichte Anstiege von Wallachen und Stuten, während die eh geringe Hengstanzahl weiter abnahm. Warmblüter bildeten mit 56,3 % die größte Rassegruppe. Über die Jahre nahm ihr prozentualer Anteil ab, während Kleinpferde zunahmen (p < 0,0001). Die stationäre Aufenthaltsdauer reduzierte sich signifikant (p < 0,01) von im Median 5,0 Tagen (2000-2002) auf 3,2 Tage (2018-2020). Der ganz überwiegende Anteil (83,5 %) der Patienten wurde einmalig vorgestellt, 11,9 % hatten mindestens eine Wiedervorstellung aufgrund der selben Erkrankung und 4,6 % wurden aufgrund anderer Symptome erneut vorgestellt. Die meisten Patienten wiesen ein perakutes Geschehen auf, dabei handelte es sich ganz überwiegend um Koliker. 67,4 % aller Patienten konnten entlassen werden, 18,6 % wurden in die Klinik für Pferde, Chirurgie und Orthopädie (PFC) ganz überwiegend (91 %) zur Kolikoperation überwiesen. In der PFI mussten 13,2 % der Patienten euthanasiert werden, 0,2 % verstarben und 0,3 % wurden in externe Kliniken überwiesen. Die Überweisungen in die PFC nahmen über die Zeit ab, während der Anteil an euthanasierten und verstorbenen Patienten zunahm, was mit dem höheren Alter der Patienten zusammenhängen könnte. Die Erkrankungen des Verdauungstraktes überwogen mit 9.039 Fällen (66,7 %). Diese wurden überwiegend durch Koliker repräsentiert. Magenerkrankungen stiegen von 11 Fällen in den ersten drei Jahren auf 193 Fälle in den letzten 3 Jahren des betrachteten Zeitraums deutlich an. Respiratorische Erkrankungen waren mit 1.558 Fällen (11,5 %) die zweit größte Hauptgruppe mit der chronisch obstruktiven Bronchitis (Equines Asthma) als häufigster Diagnose innerhalb der Atemwegserkrankungen (61,9 %). Das Herzkreislaufsystem war in 795 Fällen (5,9 %) betroffen, wobei sich von 634 kardialen Fällen 400 als Herzklappeninsuffizienzen erwiesen. Die Sammelgruppe der systemisch erkrankten Pferde machte mit 4,0 % (n = 544) aller Patienten die viert größte Gruppe aus, am häufigsten wurden hier Patienten mit Fieber (39,3 %) und Abmagerung (16,7 %) unklarer Genese einsortiert. Die Erkrankungen von Haut, Haaren und Lymphknoten kamen in 2,2 % der Gesamterkrankungen vor (302 Fälle). Die Einteilung im ersten Diagnoseschlüssel führte dazu, dass die Infektion der Lymphknoten mit Streptococcus equi. ssp. equi (Druse) 22,2 % der Patienten dieser Gruppe ausmachte. Harn- und Geschlechtsorgane waren in 242 Fällen (1,8 %) betroffen, wobei ein Anstieg von Niereninsuffizienzen von 5 Patienten in den ersten drei Jahren auf 24 Fälle in den letzten drei Jahren des betrachteten Zeitraums auffiel. In die weiteren sieben Hauptgruppen wurden zwischen 58 und 229 Fälle eingeteilt. Auf Basis dieser Auswertungen und inspiriert von der internationalen statistischen Klassifikation der Krankheiten und verwandter Gesundheitsprobleme der Weltgesundheitsorganisation (WHO) erfolgte eine Optimierung des ersten Diagnoseschlüssels. Hauptgruppen wie Haut/Haare und Lymphknoten, Herz/Kreislauf sowie Harn- und Geschlechtsapparat wurden geteilt, neue Hauptgruppen für Lymph- und Blutsystem, Sinnesorgane und Ernährungsstörungen geschaffen und zahlreiche Diagnosen ergänzt. Zudem können darin Vergiftungen, Verhaltensstörungen und unerwünschte Arzneimittelwirkungen klassifiziert werden. Die Anwendung des optimierten Diagnoseschlüssels in Pferdepraxen und –kliniken könnte maßgeblich dazu beitragen, basierend auf hohen Fallzahlen exakte Kenntnisse zu Diagnosehäufigkeiten in der Pferdemedizin zu erlangen, um daraus Forschungs- wie Ausbildungsschwerpunkte abzuleiten.