contribution to the history of animal diseases

Deckblatt-Impressum Inhaltsverzeichnis Abkürzungsverzeichnis Einleitung Material und Methodik Altertum ca. 3000 v. Chr. - 500 n. Chr. Mittelalter ca. 500 1500 n. Chr. Neuzeit ca. 1500 1830 Neuere Zeit ca. 1830 - 1900 Zusammenfassende Diskussion Zusammenfassung Summary Literaturverzeichnis Anhang Danksagung SelbständigkeitserklärungDie Geschichte der Schweinekrankheiten und deren Bekämpfung, speziell der KSP, wird von Anbeginn der literarischen Erfassung bis zum Zeitpunkt der Erkennung der Virusätiologie der KSP zu Beginn des 20. Jahrhunderts dargestellt. Die Arbeit ist untergliedert nach zeitgeschichtlichen Epochen, in denen zum besseren Verständnis der jeweiligen Ereignisse die politisch-territorialen, wirtschaftlichen, wissenschaftlichen, medizinischen und veterinärmedizinischen Verhältnisse näher beleuchtet werden. In den spärlichen antiken und mittelalterlichen Aufzeichnungen läßt sich kaum Wissenswertes über Schweinekrankheiten und deren Behandlungen finden. Die wenigen Überlieferungen, die aus diesen Perioden zur Verfügung stehen, lassen zudem einen großen Spielraum für Spekulationen. Dagegen erhöht sich die Aussagekraft der literarischen Quellen seit der Neuzeit deutlich. Ab diesem Zeitpunkt wird versucht, ein umfassendes Bild über das Vorkommen und den entsprechenden Wissensstand der wichtigsten bekannten Krankheiten zu vermitteln. Weiterhin werden verschiedenste Theorien der Krankheitsentstehung, des Wesens von Krankheiten sowie allgemeine und spezielle Therapie- und Prophylaxemaßnahmen im Wandel der Geschichte dargestellt. Mit Erfassung der ersten dokumentierten Fälle von KSP wird versucht, das Vorkommen, die Verbreitung, mögliche frühere Fälle sowie anfängliche Behandlungsversuche nachzuvollziehen. Es werden verschiedene Ursprungstheorien besprochen. Die Arbeit zeigt weiterhin den wichtigen Prozeß der Abtrennung der KSP von anderen Krankheiten. Auf die Entdeckung der Virusnatur des Erregers durch de Schweinitz und Dorset zu Beginn des 20. Jahrhunderts wird näher eingegangen. Besprochen werden außerdem die richtungweisenden Arbeiten von Loeffler, dessen Entdeckung des Erregers der MKS 1898 die Geburtsstunde der Virologie markierte. Die Bekämpfungsversuche, die aufgrund der falschen ätiologischen Voraussetzung kaum relevante Erfolge zu verzeichnen hatten, konzentrierten sich im Wesentlichen auf veterinärpolizeiliche und hygienische, serologische sowie medikamentöse Maßnahmen. Das schon frühzeitig von verschiedenen Wissenschaftlern favorisierte veterinärpolizeiliche Vorgehen zeigte lange Zeit nicht die erwarteten Erfolge, was sich durch fehlende überregionale Regelung der Maßnahmen erklären läßt. Erst die Erkenntnis der Virusätiologie brachte neue Impulse für die nun stärker im Vordergrund stehende Immunprophylaxe und -therapie sowie die veterinärpolizeiliche Handhabung. Abschließend wird auf den derzeitigen Stand sowie aktuelle und zukünftige Probleme der KSP- Bekämpfung eingegangen.The history of swine diseases and their control, particularly that of classical swine fever, is described from the first recordings to the time of elucidation of the etiology of the classical swine fever virus at the beginning of the 20 th century. The work is subdivided according to the historical epochs. For a better understanding of the listed events the political-territorial, economic, scientific, medical and veterinary conditions of the respective epochs are described in greater detail. In the scare antique and medieval recordings little information can be found on swine diseases and their treatment. In addition, the few recordings from these epochs leave a lot of room for speculation. In contrast, the informational value of the literary sources increases significantly in modern times. From this time on efforts are made to provide an extensive overview of the occurrence of and the knowledge on the most important diseases known. In addition, a great diversity of theories on the pathogenesis and on the nature of diseases as well as general and specific therapeutic and prophylactical measures developed over the years are described. Starting with the first cases documented it is tried to reconstruct the occurrence and spread of CSF as well as the occurrence of possible earlier cases and early therapeutic attempts. A diversity of theories on the origins of the disease is discussed. Furthermore, the work shows the important process of differentiating CSF from other diseases. The elucidation of the nature of the virus by de Schweinitz and Dorset at the beginning of the 20 th century is decribed in greater detail. In addition, the ground-breaking works of Loeffler are discussed, whose discovery of the causative agent of foot-and-mouth disease in 1898 marked the birth of the science of virology. Attempts to control the disease which were based on wrong assumption on the etiology of the virus and therefore largely remaind unsuccessful basically concentrated on general and veterinary hygienic, serological and medicinal measures. The application of veterinary hygienic measures, which was favoured by various scientists already at an early stage, did not lead to the expected positive effects, which can be explained by the fact that the measures were not coordinated at a sopra-regional level. New impulses for immune prophylaxis and therapy as well as for the veterinary hygienic handling of the disease first came from the elucidation of the etiology of the virus. Finally, the present situation as well as present and future problems of CSF control are dicussed

Novel role of Ras-GTPase Activating Protein SH3 Domain-Binding Protein G3BP in adhesion and migration of 32D myeloid progenitor cells

Rho GTPases are involved in homing and mobilization of hematopoietic stem and progenitor cells due to their impact on cytoskeleton remodeling. We have previously shown that inhibition of Rho, Rac and Cdc42 clearly impairs adhesion of normal and leukemic hematopoietic progenitor cells (HPC) to fibronectin and migration in a three-dimensional stromal cell model. Here, we identified the Ras GTPase-Activating Protein SH3 Domain-Binding Protein (G3BP) as a target gene of Rho GTPases and analysed its role in regulating HPC motility. Overexpression of G3BP significantly enhanced adhesion of murine 32D HPC to fibronectin and human umbilical vein endothelial cells, increased the proportion of adherent cells in a flow chamber assay and promoted cell migration in a transwell assay and a three-dimensional stromal cell model suggesting a strong impact on the cytoskeleton. Immunofluorescent staining of G3BP-overexpressing fibroblasts revealed a Rho-like phenotype characterized by formation of actin stress fibers in contrast to the Rac-like phenotype of control fibroblasts. This is the first report implicating a role for G3BP in Rho GTPase-mediated signalling towards adhesion and migration of HPC. Our results may be of clinical importance, since G3BP was found overexpressed in human cancers

A Computed Tomographic Study of the Premolar Teeth of Babyrousa spp.

A photographic and computed tomography (CT) scanning study was carried out on the premolar teeth of 18 adult male Babyrousa babyrussa skulls, 10 skulls of Babyrousa celebensis, including 6 adult males, 1 adult female, 1 subadult male, 1 subadult female, and 1 juvenile male. The occlusal morphology of the permanent maxillary premolar teeth of B. babyrussa was very similar to that of B. celebensis. Almost all the maxillary third premolar teeth (107/207) had 2 roots, whereas maxillary fourth premolar teeth (108/208) had 3 or 4 roots. All of the mesial tooth roots of 107/207 and 108/208 were tapering rod-like structures; each contained a single pulp canal. Almost all distal roots of 107/207 were “C” shaped and contained 2 pulp canals. The 108/208 palatal roots were “C” shaped and contained 2 pulp canals. The mesial and distal roots of the mandibular third premolar teeth (307/407) teeth were uniformly rod-like, as were the mesial roots of the mandibular fourth premolar teeth (308/408) teeth. The distal roots of the 308/408 teeth were “C” shaped. All B. babyrussa 307/407 teeth have a single pulp canal located in each of the mesial and distal roots. The 308/408 mesial tooth root contained 1 pulp canal. In all but 3 of the 36 distal 308/408 roots of B. babyrussa teeth and in 7 of the 14 distal roots of B. celebensis teeth there was a single pulp canal; in the other 7 teeth there were 2 pulp canals. Each of the 3 medial roots contained 1 pulp canal

Biological characterization of Poly-L-lactic acid (PLLA)/Hydroxyapatite (HA)/Bioglass (BG) composite scaffolds made by Thermally Induced Phase Separation (TIPS) hosting human Mesenchymal Stem Cells

In the last few years, Tissue Engineering has focused on the favourable effects that composite scaffolds have on cell adhesion, growth and differentiation. In fact, composite scaffolds, usually composed of a synthetic polymer supplemented with naturally occurring components, display superior mechanical properties and bioconductivity than scaffolds consisting of a single component. Hydroxyapatite (HA) is the major inorganic component of bones. Bioglass (BG) is known to exert stimulatory effects on cells by ion release and hence, could be also advantageous for Bone Tissue Engineering. Poly-L-lactic acid (PLLA) is a versatile synthetic polymer combinable with HA and BG. The aim of this work was to assess the effectiveness of PLLA/HA and PLLA/HA/BG 1393 composite scaffolds as suitable artificial Extracellular Matrix (ECM) for human Mesenchymal Stromal Cells (h-MSCs). In order to check if composite scaffolds are actually superior, a comparison was made between the scaffolds above mentioned and PLLA and PLLA/BG scaffolds. All four types of scaffolds (PLLA, PLLA/HA, PLLA/BG and PLLA/HA/BG) were manufactured in Palermo, at the University of Palermo, using the Thermally Induced Phase Separation (TIPS) technique, for which a PLLA/1,4-dioxane/water ternary solution was chosen. In composite scaffolds, HA and BG 1393 were added in the solution as powder phase. The temperature selected for promoting the phase separation was 30 °C and the residence time in the thermostatic bath was set to 80 minutes. The samples were then placed in a cooling bath at -20 °C for 15 minutes, in order to freeze the porous structure thus formed. With these process conditions, scaffolds with a porosity higher than 90% and a mean pore size of 100 μm were obtained. After subsequent washing and drying steps, the as-obtained cylindrical structures were cut in disk-shaped specimens with a diameter of 6 mm and a thickness of 1.5 mm. Before the seeding stage, scaffolds were sterilized in 70% ethanol solution, stored in Phosphate Buffered Saline (PBS) and finally soaked in h-MSCs culture medium. The seeding of h-MSCs occurred in a 96-well plate and monitoring analyses were carried out at time points of 48 hours and 8 days. Before used for seeding experiments, undifferentiated MSCs were characterized for a set of markers (CD34, CD44, CD45, CD90, CD105, Vimentin) to show their typical expression pattern before seeding. Multilineage differentiation potential was proven by adipogenic, osteogenic and chondrogenic differentiation. Life/dead assays, Haematoxylin/Eosin, Alcian blue and Alizarin red stainings were employed to verify cells viability, ECM synthesis, adhesion to the polymeric structure and migration into the scaffold. Cell proliferation was calculated from DNA content using CyQuant assay. h-MSCs expressed the typical markers, they were able to spread evenly on both upper and lower surfaces of all types of scaffold. The majority of the adhering cells survived on the scaffolds over the whole observation period. Scaffolds supplemented with HA revealed a higher seeded area compared with PLLA and BG alone. Furthermore, h-MSCs penetrated in mean 260 µm into the porous polymeric structure of all scaffolds. The next step will involve long time experiments with h-MSCs under osteogenic and non-osteogenic conditions in the same types of scaffolds. Successful osteogenic differentiation will be tested by monitoring osteogenic marker expression, e.g. type X collagen

Ebola Outbreak Containment: Real-Time Task and Resource Coordination With SORMAS

Background: Since the beginning of the Ebola outbreak in West Africa in 2014, more than 11,000 people died. For outbreaks of infectious diseases like this, the rapid implementation of control measures is a crucial factor for containment. In West African countries, outbreak surveillance is a paper-based process with significant delays in forwarding outbreak information, which affects the ability to react adequately to situational changes. Our objective therefore was to develop a tool that improves data collection, situation assessment, and coordination of response measures in outbreak surveillance processes for a better containment. Methods: We have developed the Surveillance and Outbreak Response Management System (SORMAS) based on findings from Nigeria's 2014 Ebola outbreak. We conducted a thorough requirements engineering and defined personas and processes. We also defined a data schema with specific variables to measure in outbreak situations. We designed our system to be a cloud application that consists of interfaces for both mobile devices and desktop computers to support all stakeholders in the process. In the field, health workers collect data on the outbreak situation via mobile applications and directly transmit it to control centers. At the control centers, health workers access SORMAS via desktop computers, receive instant updates on critical situations, react immediately on emergencies, and coordinate the implementation of control measures with SORMAS. Results: We have tested SORMAS in multiple workshops and a field study in July 2015. Results from workshops confirmed derived requirements and implemented features, but also led to further iterations on the systems regarding usability. Results from the field study are currently under assessment. General feedback showed high enthusiasm about the system and stressed its benefits for an effective outbreak containment of infectious diseases. Conclusions: SORMAS is a software tool to support health workers in efficiently handling outbreak situations of infectious diseases, such as Ebola. Our tool enables a bi-directional exchange of situational data between individual stakeholders in outbreak containment. This allows instant and seamless collection of data from the field and its instantaneous analysis in operational centers. By that, SORMAS accelerates the implementation of control measures, which is crucial for a successful outbreak containment.Peer Reviewe

Refphase: Multi-sample phasing reveals haplotype-specific copy number heterogeneity

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient’s disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase’s ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours

The Pheno- and Genotypic Characterization of Porcine Escherichia coli Isolates

Escherichia (E.) coli is the main causative pathogen of neonatal and post-weaning diarrhea and edema disease in swine production. There is a significant health concern due to an increasing number of human infections associated with food and/or environmental-borne pathogenic and multidrug-resistant E. coli worldwide. Monitoring the presence of pathogenic and antimicrobial-resistant E. coli isolates is essential for sustainable disease management in livestock and human medicine. A total of 102 E. coli isolates of diseased pigs were characterized by antimicrobial and biocide susceptibility testing. Antimicrobial resistance genes, including mobile colistin resistance genes, were analyzed by PCR and DNA sequencing. The quinolone resistance-determining regions of gyrA and parC in ciprofloxacin-resistant isolates were analyzed. Clonal relatedness was investigated by two-locus sequence typing (CH clonotyping). Phylotyping was performed by the Clermont multiplex PCR method. Virulence determinants were analyzed by customized DNA-based microarray technology developed in this study for fast and economic molecular multiplex typing. Thirty-five isolates were selected for whole-genome sequence-based analysis. Most isolates were resistant to ampicillin and tetracycline. Twenty-one isolates displayed an ESBL phenotype and one isolate an AmpC β-lactamase-producing phenotype. Three isolates had elevated colistin minimal inhibitory concentrations and carried the mcr-1 gene. Thirty-seven isolates displayed a multi-drug resistance phenotype. The most predominant β-lactamase gene classes were blaTEM-1 (56%) and blaCTX-M-1 (13.71%). Mutations in QRDR were observed in 14 ciprofloxacin-resistant isolates. CH clonotyping divided all isolates into 51 CH clonotypes. The majority of isolates belonged to phylogroup A. Sixty-four isolates could be assigned to defined pathotypes wherefrom UPEC was predominant. WGS revealed that the most predominant sequence type was ST100, followed by ST10. ST131 was detected twice in our analysis. This study highlights the importance of monitoring antimicrobial resistance and virulence properties of porcine E. coli isolates. This can be achieved by applying reliable, fast, economic and easy to perform technologies such as DNA-based microarray typing. The presence of high-risk pathogenic multi-drug resistant zoonotic clones, as well as those that are resistant to critically important antibiotics for humans, can pose a risk to public health. Improved protocols may be developed in swine farms for preventing infections, as well as the maintenance and distribution of the causative isolates

The Pheno- and Genotypic Characterization of Porcine Escherichia coli Isolates

Escherichia (E.) coli is the main causative pathogen of neonatal and post-weaning diarrhea and edema disease in swine production. There is a significant health concern due to an increasing number of human infections associated with food and/or environmental-borne pathogenic and multidrug-resistant E. coli worldwide. Monitoring the presence of pathogenic and antimicrobial-resistant E. coli isolates is essential for sustainable disease management in livestock and human medicine. A total of 102 E. coli isolates of diseased pigs were characterized by antimicrobial and biocide susceptibility testing. Antimicrobial resistance genes, including mobile colistin resistance genes, were analyzed by PCR and DNA sequencing. The quinolone resistance-determining regions of gyrA and parC in ciprofloxacin-resistant isolates were analyzed. Clonal relatedness was investigated by two-locus sequence typing (CH clonotyping). Phylotyping was performed by the Clermont multiplex PCR method. Virulence determinants were analyzed by customized DNA-based microarray technology developed in this study for fast and economic molecular multiplex typing. Thirty-five isolates were selected for whole-genome sequence-based analysis. Most isolates were resistant to ampicillin and tetracycline. Twenty-one isolates displayed an ESBL phenotype and one isolate an AmpC β-lactamase-producing phenotype. Three isolates had elevated colistin minimal inhibitory concentrations and carried the mcr-1 gene. Thirty-seven isolates displayed a multi-drug resistance phenotype. The most predominant β-lactamase gene classes were blaTEM-1 (56%) and blaCTX-M-1 (13.71%). Mutations in QRDR were observed in 14 ciprofloxacin-resistant isolates. CH clonotyping divided all isolates into 51 CH clonotypes. The majority of isolates belonged to phylogroup A. Sixty-four isolates could be assigned to defined pathotypes wherefrom UPEC was predominant. WGS revealed that the most predominant sequence type was ST100, followed by ST10. ST131 was detected twice in our analysis. This study highlights the importance of monitoring antimicrobial resistance and virulence properties of porcine E. coli isolates. This can be achieved by applying reliable, fast, economic and easy to perform technologies such as DNA-based microarray typing. The presence of high-risk pathogenic multi-drug resistant zoonotic clones, as well as those that are resistant to critically important antibiotics for humans, can pose a risk to public health. Improved protocols may be developed in swine farms for preventing infections, as well as the maintenance and distribution of the causative isolates