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- I-5818-2014 (1)
Bacterial mastitis is caused by invasion of the udder, bacterial multiplication and induction of
inflammatory responses in the bovine mammary gland. Disease severity and the cause of disease are
influenced by environmental factors, the cow’s immune response as well as bacterial traits. Escherichia coli (E. coli) is one of the main causes of acute bovine mastitis, but although pathogenic E. coli strains can be classified into different pathotypes, E. coli causing mastitis cannot unambiguously be distinguished from commensal E. coli nor has a common set of virulence factors
been described for mastitis isolates. This project focussed on the characterization of virulence-
associated traits of E. coli mastitis isolates in comprehensive analyses under conditions either
mimicking initial pathogenesis or conditions that E. coli mastitis isolates should encounter while entering the udder. Virulence-associated traits as well as fitness traits of selected bovine mastitis or faecal E. coli strains were identified and analyzed in comparative phenotypic assays. Raw milk whey was introduced to
test bacterial fitness in native mammary secretion known to confer antimicrobial effects.
Accordingly, E. coli isolates from bovine faeces represented a heterogeneous group of which some
isolates showed reduced ability to survive in milk whey whereas others phenotypically resembled
mastitis isolates that represented a homogeneous group in that they showed similar survival and
growth characteristics in milk whey. In contrast, mastitis isolates did not exhibit such a uniform phenotype when challenged with iron shortage, lactose as sole carbon source and lingual
antimicrobial peptide (LAP) as a main defensin of milk. Reduced bacterial fitness could be related to LAP suggesting that bacterial adaptation to an intramammary lifestyle requires resistance to host
defensins present in mammary secretions, at least LAP.
E. coli strain 1303 and ECC-1470 lack particular virulence genes associated to mastitis isolates. To find out whether differences in gene expression may contribute to the ability of E. coli variants to cause mastitis, the transcriptome of E. coli model mastitis isolates 1303 and ECC-1470 were analyzed to
identify candidate genes involved in bacterium-host interaction, fitness or even pathogenicity during bovine mastitis.
DNA microarray analysis was employed to assess the transcriptional response of E. coli 1303 and
ECC-1470 upon cocultivation with MAC-T immortalized bovine mammary gland epithelial cells to
identify candidate genes involved in bacterium-host interaction. Additionally, the cell adhesion and invasion ability of E. coli strain 1303 and ECC-1470 was investigated. The transcriptonal response to the presence of host cells rather suggested competition for nutrients and oxygen between E. coli and MAC-T cells than marked signs of adhesion and invasion. Accordingly, mostly fitness traits that may also contribute to efficient colonization of the E. coli primary habitat, the gut, have been utilized by the mastitis isolates under these conditions. In this study, RNA-Seq was employed to assess the bacterial transcriptional response to milk whey.
According to our transcriptome data, the lack of positively deregulated and also of true virulence-associated determinants in both of the mastitis isolates indicated that E. coli might have adapted by other means to the udder (or at least mammary secretion) as an inflammatory site. We identified traits that promote bacterial growth and survival in milk whey. The ability to utilize citrate promotes fitness and survival of E. coli that are thriving in mammary secretions. According to our results, lactoferrin has only weak impact on E. coli in mammary secretions. At the same time bacterial determinants involved in iron assimilation were negatively regulated, suggesting that, at least during the first hours, iron assimilation is not a challenge to E. coli colonizing the mammary gland. It has been hypothesized that cellular iron stores cause temporary independency to extracellular accessible iron. According to our transcriptome data, this hypothesis was supported and places iron uptake
systems beyond the speculative importance that has been suggested before, at least during early
phases of infection. It has also been shown that the ability to resist extracytoplasmic stress, by oxidative conditions as well as host defensins, is of substantial importance for bacterial survival in mammary secretions.
In summary, the presented thesis addresses important aspects of host-pathogen interaction and
bacterial conversion to hostile conditions during colonization of the mastitis inflammatory site, the mammary gland.
Diese Arbeit beschäftigt sich mit der Evaluation eines Computerprogramms zur Leseförderung anhand einer ausgewählten Gruppe von Drittklässlern der Diagnose- und Förderklassen. Ausgewählt wurde das celeco-Programm (celeco - Richtig Lesen Lernen). Das Anliegen dieser Arbeit ist die Evaluation des celeco-Programms hinsichtlich seiner Wirksamkeit und Anwendbarkeit im Bereich der Leseförderung bei leseschwachen Schülern mit sonderpädagogischem Förderbedarf.
Dabei wurde folgendes Vorgehen gewählt: Eine Reihe schwacher Leser wurde mit dem oben erwähnten Programm im Leselernprozess gefördert. Es wurden Ausgangsdaten und Daten über die Lernfortschritte der Probanden gesammelt. Die Kontrollgruppe bildeten die nicht geförderten Klassenkameraden.
In einer anschließenden statistischen Auswertung wurde untersucht, ob das gewählte Förderprogramm erfolgreich angewendet werden konnte und sich somit als effektiv erwies.
Die Auswertung zeigte, dass die geförderten Kinder sich in den trainierten Aufgaben signifikant verbesserten und eine Steigerung der Lesegenauigkeit stattfand, die auch außerhalb des Computerprogramms nachweisbar war. Bei den Kindern der Kontrollgruppe konnte im Förderzeitraum keine Verbesserung der Lesegenauigkeit im gleichen Ausmaß festgestellt werden. Besonders günstig wirkte sich das Training auf die Leser aus, die das simultane Erfassen mehrerer Buchstaben nicht beherrschten.
Beim celeco-Programm scheint es sich demnach um ein effektives Computerprogramm zur Leseförderung von leseschwachen Schülern mit sonderpädagogischem Förderbedarf zu handeln.
Healthy Dietary Interventions and Lipoprotein (a) Plasma Levels: Results from the Omni Heart Trial
(2014)
Background: Increased lipoprotein(a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Studies of dietary interventions on changes in Lp(a) are sparse. We aimed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a) concentration.
Methods: Secondary analysis of a randomized, 3-period crossover feeding study including 155 (89 blacks; 66 whites) individuals. Participants were given DASHtype healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each diet.
Results: Compared to baseline, all interventional diets increased mean Lp(a) by 2 to 5 mg/dl. Unsat Fat increased Lp(a) less than Prot with a difference of 1.0 mg/dl (95% CI, -0.5, 2.5; p=0.196) in whites and 3.7 mg/dl (95% CI, 2.4, 5.0; p<0.001) in blacks (p-value between races=0.008); Unsat Fat increased Lp(a) less than Carb with a difference of 20.6 mg/dl, 95% CI, -2.1, 0.9; p=0.441) in whites and 21.5 mg/dl (95% CI, -0.2, -2.8; p=0.021) in blacks (p-value between races=0.354). Prot increased Lp(a) more than Carb with a difference of 0.4 mg/dl (95% CI, -1.1, 1.9; p=0.597) in whites and 2.2 mg/dl (95%CI, 0.9, 3.5; p=0.001) in blacks (p-value between races=0.082).
Conclusion: Diets high in unsaturated fat increased Lp(a) levels less than diets rich in carbohydrate or protein with greater changes in blacks than whites. Our results suggest that substitutions with dietary mono- and polyunsaturated fatty acids in healthy diets may be preferable over protein or carbohydrates with regards to Lp(a).