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Risk Assessment of Chlorogenic and Isochlorogenic Acids in Coffee By-Products
No full textChlorogenic and isochlorogenic acids are naturally occurring antioxidant dietary polyphenolic compounds found in high concentrations in plants, fruits, vegetables, coffee, and coffee by-products. The objective of this review was to assess the potential health risks associated with the oral consumption of coffee by-products containing chlorogenic and isochlorogenic acids, considering both acute and chronic exposure. An electronic literature search was conducted, revealing that 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-DCQA) are the major chlorogenic acids found in coffee by-products. Toxicological, pharmacokinetic, and clinical data from animal and human studies were available for the assessment, which indicated no significant evidence of toxic or adverse effects following acute oral exposure. The current state of knowledge suggests that long-term exposure to chlorogenic and isochlorogenic acids by daily consumption does not appear to pose a risk to human health when observed at doses within the normal range of dietary exposure. As a result, the intake of CQAs from coffee by-products can be considered reasonably safe
Umlaut and allomorphy as diagnostics in the analysis of suspended affixation: Experimental evidence from acceptability judgments
No full textThis thesis investigates the phenomenon of suspended affixation (Lewis 1967) and its interaction with umlaut and allomorphy in order to identify its underlying structure. The bringing together of these affixation phenomena fills an empirical gap in German and is a novel attempt to base the analysis of suspended affixation on well-founded assumptions. The thesis focuses on differentiating two types of analyses that have been proposed in the analysis of suspended affixation: deletion (e.g. Booij 1985, Wiese 1992, Erschler 2012) and base generation (e.g. Hankamer 2012, Yoon 2017). The two analyses differ in terms of their underlying structure.
A deletion analysis assumes that the suspended affix is present in the underlying structure and only deleted at the surface. In contrast, a base generation analysis assumes that the only affix in the underlying structure is the surface affix. In this thesis, I examine the predictions of the underlying structures of the two analysis types with regard to other affixation phenomena.
The two analysis types differ in the presence or absence of an underlying affix. Given the existence of an underlying affix, it is expected that affixation phenomena such as stem changes will surface in the context of suspended affixation under a deletion analysis, but not under a base generation analysis. I tested these predictions using the phenomenon of umlaut in German, which represents an example of a stem change that is triggered during affixation. The acceptability of umlaut in the context of suspended affixation was evaluated through experimental data collection. The resulting empirical and statistical evidence supports the conclusion that umlaut does not affect the acceptability of suspended affixation. The experimental data confirms the predictions of a deletion analysis and suggests that suspended affixes are present in the underlying structure. Theoretically, it can be concluded that suspended affixation results from deletion. The assumption that this deletion is predominantly phonological is
supported by the experimental investigation of another affixation phenomenon in this thesis, namely allomorphy. The data on allomorphy indicate that the acceptability of suspended affixation is negatively affected by a lack of phonological identity. However, the negative effect of mismatching allomorphs in the context of suspended affixation further reveals an ordering effect. The order of the mismatching allomorphs has a significant effect on the acceptability of suspended affixation. A purely phonological deletion could not account for this asymmetry. I therefore conclude that suspended affixation is a surface phenomenon which can be derived from different underlying structures within one language. I propose an analysis in the frameworks of Distributed Morphology (Halle & Marantz 1993, Halle & Marantz 1994) and Harmonic Grammar (Legendre, Miyata, & Smolensky 1990). The analysis is located at spell-out, where morpho-syntactic structure, lexical entries and phonological processes give
rise to both, deletion and base generation derivations of suspended affixation. Deletion arises as an option during optimization. Base generation is analyzed as affixation to a coordination phrase. This thesis demonstrates the complexity of the empirical pattern of suspended affixation, a phenomenon of the interfaces. Furthermore, the investigation of its interaction with other affixation phenomena allows to delimit the availability of derivations by establishing the available underlying structures.:Abstract
Acknowledgments
Table of contents
List of symbols and abbreviations
List of Figures
List of Tables
1Introduction
2 Umlaut, a stem change diagnostic
2.1 The stem change diagnostic
2.2 Umlaut in German
2.3 Research questions and hypotheses
2.4 Operationalization
2.4.1 Items
2.4.2 Survey design
2.4.3 Procedure and participants
2.5 Statistical analysis
2.5.1 Generalizations
2.5.2 Discussion
2.5.3 Outliers
3 Allomorphy, an identity diagnostic
3.1 The identity diagnostic
3.2 Allomorphy in German
3.3 Research question and hypotheses
3.4 Operationalization
3.5 Statistical analysis
3.5.1 Generalizations
3.5.2 Discussion
3.5.3 Outliers
4 Analysis
4.1 Aim of the analysis
4.2 Previous analyses
4.3 Framework and assumptions
4.4 Suspension from phonological word deletion
4.5 Suspension from base generation
4.6 Summary
4.7 Other analyses in the literature
5 Implications
5.1 Two, converging derivations
5.2 Suspended suffix combinations
5.3 The coordination of three conjuncts
5.4 The analysis of suspended compounding
5.5 The analysis of umlaut
6 Conclusion
Appendix A
Referenc
Development of an AI based automated analysis of pediatric Apple Watch iECGs
No full textIntroduction: The Apple Watch valuably records event-based electrocardiograms
(iECG) in children, as shown in recent studies by Paech et al. In contrast to adults,
though, the automatic heart rhythm classification of the Apple Watch did not
provide satisfactory results in children. Therefore, ECG analysis is limited to
interpretation by a pediatric cardiologist. To surmount this difficulty, an artificial
intelligence (AI) based algorithm for the automatic interpretation of pediatric
Apple Watch iECGs was developed in this study.
Methods: A first AI-based algorithm was designed and trained based on
prerecorded and manually classified i.e., labeled iECGs. Afterward the algorithm
was evaluated in a prospectively recruited cohort of children at the Leipzig
Heart Center. iECG evaluation by the algorithm was compared to the 12-lead-
ECG evaluation by a pediatric cardiologist (gold standard). The outcomes were
then used to calculate the sensitivity and specificity of the Apple Software and
the self-developed AI.
Results: The main features of the newly developed AI algorithm and the rapid
development cycle are presented. Forty-eight pediatric patients were enrolled in
this study. The AI reached a specificity of 96.7% and a sensitivity of 66.7% for
classifying a normal sinus rhythm.
Conclusion: The current study presents a first AI-based algorithm for the
automatic heart rhythm classification of pediatric iECGs, and therefore provides
the basis for further development of the AI-based iECG analysis in children as
soon as more training data are available. More training in the AI algorithm is
inevitable to enable the AI-based iECG analysis to work as a medical tool in
complex patients
Meteorologische Arbeiten (XXX) und Jahresbericht 2024 des Instituts für Meteorologie der Universität Leipzig
No full textFeline Infectious Peritonitis: European Advisory Board on Cat Diseases Guidelines
No full textFeline coronavirus (FCoV) is a ubiquitous RNA virus of cats, which is transmitted faeco-orally. In these guidelines, the European Advisory Board on Cat Diseases (ABCD) presents a comprehensive review of feline infectious peritonitis (FIP). FCoV is primarily an enteric virus and most infections do not cause clinical signs, or result in only enteritis, but a small proportion of FCoV-infected cats develop FIP. The pathology in FIP comprises a perivascular phlebitis that can affect any organ. Cats under two years old are most frequently affected by FIP. Most cats present with fever, anorexia, and weight loss; many have effusions, and some have ocular and/or neurological signs. Making a diagnosis is complex and ABCD FIP Diagnostic Approach Tools are available to aid veterinarians. Sampling an effusion, when present, for cytology, biochemistry, and FCoV RNA or FCoV antigen detection is very useful diagnostically. In the absence of an effusion, fine-needle aspirates from affected organs for cytology and FCoV RNA or FCoV antigen detection are helpful. Definitive diagnosis usually requires histopathology with FCoV antigen detection. Antiviral treatments now enable recovery in many cases from this previously fatal disease; nucleoside analogues (e.g., oral GS-441524) are very effective, although they are not available in all countries
Successional shifts in tree demographic strategies in wet and dry Neotropical forests
No full textAim: Tropical forest succession and associated changes in community composition
are driven by species demographic rates, but how demographic strategies shift dur-
ing succession remains unclear. Our goal was to identify generalities in demographic
trade-offs and successional shifts in demographic strategies across Neotropical for-
ests that cover a large rainfall gradient and to test whether the current conceptual
model of tropical forest succession applies to wet and dry forests.
Location: Mexico and Central America.
Time period: 1985– 2018.
Major taxa studied: Trees.
Methods: We used repeated forest inventory data from two wet and two dry forests
to quantify demographic rates of 781 tree species. For each forest, we explored the
main demographic trade-offs and assigned tree species to five demographic groups
by performing a weighted principal components analysis to account for differences in
sample size. We aggregated the basal area and abundance across demographic groups
to identify successional shifts in demographic strategies over the entire successional
gradient from very young (<5 years) to old-growth forests.
Results: Across all forests, we found two demographic trade-offs, namely the
growth–survival trade-off and the stature–recruitment trade-off, enabling the data-
driven assignment of species to five demographic strategies. Fast species dominated
early in succession and were then replaced by long-lived pioneers in three forests.
Intermediate and slow species increased in basal area over succession in all forests,
but, in contrast to the current conceptual model, long-lived pioneers continued to
dominate until the old-growth stage in all forests. The basal area of short-lived breed-
ers was low across all successional stages.
Main conclusions: The current conceptual model of Neotropical forest succes-
sion should be revised to incorporate the dominance of long-lived pioneers in
late-successional and old-growth forests. Moreover, the definition of consistent de-
mographic strategies that show clear dominance shifts across succession substan-
tially improves the mechanistic understanding and predictability of Neotropical forest
succession
Membrane-bound Interleukin-1α mediates leukocyte adhesion during atherogenesis
No full textIntroduction: The interleukin-1 (IL-1) family and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome contribute to atherogenesis but the underlying mechanisms are incompletely understood. Unlike IL-1β, IL-1α is not dependent on the NLRP3 inflammasome to exert its pro-inflammatory effects. Here, a non-genetic model was applied to characterize the role of IL-1α, IL-1β, and NLRP3 for the pathogenesis of atherosclerosis.
Methods: Atherogenesis was induced by gain-of-function PCSK9-AAV8 mutant viruses and feeding of a high-fat western diet (WTD) for 12 weeks in C57Bl6/J wildtype mice (WT) and in Il1a-/-, Nlrp3-/-, and Il1b-/- mice.
Results: PCSK9-Il1a-/- mice showed reduced atherosclerotic plaque area in the aortic root with lower lipid accumulation, while no difference was observed between PCSK9-WT, PCSK9-Nlrp3-/- and PCSK9-Il1b-/- mice. Serum proteomic analysis showed a reduction of pro-inflammatory cytokines (e.g., IL-1β, IL-6) in PCSK9-Il1a-/- as well as in PCSK9-Nlrp3-/- and PCSK9-Il1b-/- mice. Bone marrow dendritic cells (BMDC) of PCSK9-WT, PCSK9-Nlrp3-/-, and PCSK9-Il1b-/- mice and primary human monocytes showed translocation of IL-1α to the plasma membrane (csIL-1α) upon stimulation with LPS. The translocation of IL-1α to the cell surface was regulated by myristoylation and increased in mice with hypercholesterolemia. CsIL-1α and IL1R1 protein-protein interaction on endothelial cells induced VCAM1 expression and monocyte adhesion, which was abrogated by the administration of neutralizing antibodies against IL-1α and IL1R1.
Conclusion: The results highlight the importance of IL-1α on the cell surface of circulating leucocytes for the development of atherosclerosis. PCSK9-Il1a-/- mice, but not PCSK9-Nlrp3-/- or PCSK9-Il1b-/- mice, are protected from atherosclerosis after induction of hypercholesterolemia independent of circulating cytokines. Myristoylation and translocation of IL-1α to the cell surface in myeloid cells facilitates leukocyte adhesion and contributes to the development of atherosclerosis
Charakterisierung molekularer Mechanismen der Tumorregression bei kaninen Neoplasien
No full textEinleitung: Krebserkrankungen sind eine der häufigsten Todesursachen bei Hund und Mensch. Das kanine kutane Histiozytom (CCH) stellt eine von den Langerhans-Zellen ausgehende Neoplasie dar, die mit einer hohen Mitosezahl sowie in den meisten Fällen mit einer Spontanregression einhergeht. Im Gegensatz dazu, zeigen Hunde mit einem histiozytären Sarkom (HS) nur kurze Überlebenszeiten, obwohl HS von ähnlichen Zellen ausgehen. Immunkontrollpunktmoleküle wie cluster of differentiation (CD)80 und CD86 dienen der Regulation der Immunantwort und werden häufig von Tumoren exprimiert. Da die genannten Tumoren sich in der Stärke der durch sie hervorgerufenen Immunantwort unterscheiden, wurde ein Zusammenhang mit der Expression der Immunkontrollpunkt-moleküle vermutet. Weiterhin bestehen laut Literatur Parallelen zwischen der antiviralen und antitumoralen Immunantwort.
Ziele der Untersuchungen: Im Rahmen der durchgeführten Untersuchungen sollten drei Fragestellungen beantwortet werden: 1.) Ist die Tumorregression beim CCH im Sinne einer vermehrten Apoptose oder einer geringeren Replikation zu verstehen? 2.) Liegen Unterschiede in der Ausprägung der Immunevasionsmechanismen beim CCH und HS vor? 3.) Spielen Mechanismen der antiviralen Immunantwort, konkret des Interferon (IFN)-Typ-I-Weges, bei der Regression des CCH eine Rolle?
Material und Methoden: Für die Untersuchungen wurden formalinfixierte und paraffineingebettete Proben von 48 CCH von 48 Hunden und insgesamt 21 HS von 15 Hunden verwendet. Die CCH wurden anhand der infiltrierenden Lymphozyten in vier Gruppen eingeteilt: Gruppe 1: keine bis geringe Anzahl an Lymphozyten, Gruppe 2: wenige bis mäßige Anzahl an Lymphozyten, Gruppe 3: mäßige bis hohe Anzahl an Lymphozyten, Gruppe 4: mehrheitlich Lymphozyten). Die HS wurden nach ihrer Lokalisation (Haut, Leber, Lunge) unterschieden. Von den Proben wurden Paraffinschnitte angefertigt und diese immunhistologisch mittels Antikörpern für gespaltene Caspase 3, CD3 (nur CCH), CD80, CD86, forkhead box protein 3 (FoxP3; nur CCH), Ki-67, MX1, programmed death ligand 1 (PD-L1), Survivin und stimulator of interferon genes (STING; nur HS) gefärbt. Weiterhin erfolgte eine in-situ Hybridisierung zum Nachweis von MX1 und IFN-γ (nur CCH). Der Anteil und die Anzahl an immunmarkierten Zellen wurde mittels der Bildanalysesoftware QuPath an Scans der Schnitte sowie lichtmikroskopisch untersucht. Die statistische Auswertung erfolgte mittels R. Q-Q-plots wurden zur Testung auf Normalverteilung genutzt. Auf Unterschiede zwischen den Gruppen und Tumoren wurden zunächst mit dem Kruskal-Wallis-Tests und post-hoc mit dem Mann-Whitney-U-Test getestet. Zur Ermittlung von Korrelationen wurde Spearman’s ρ bestimmt. Das Signifikanzniveau betrug in allen Fällen p < 0.05.
Ergebnisse: Die untersuchten Proteine wurden in allen Proben nachgewiesen. Hierbei zeigten sich Unterschiede zwischen den Gruppen des CCH, zwischen den Organen beim HS sowie zwischen den beiden Tumoren. So nahm der Anteil an CD80 positiven Tumorzellen zwischen den Gruppen des CCH signifikant ab (43,44 % in Gruppe 1 bzw. 22,38 % in
Gruppe 3), während die Zahl an Caspase-3 positiven Zellen zunahm (0,12 % in Gruppe 1 bzw.
0,55 % in Gruppe 3). Im kutanen HS wurde ein deutlich höherer Anteil an CD80 (30,8 %) als CD86 positiven Tumorzellen (3,19 %) festgestellt, während der Anteil an CD80 und C86 positiven Tumorzellen beim CCH ähnlich war (31,65 % und 25,83 % über alle Gruppen). Gleichermaßen zeigten Proben des HS aus der Lunge einen höheren Anteil an CD80 als CD86 positiven Tumorzellen (52,29 % bzw. 7,21 %), während die Anzahl an CD80 und CD86 positiven Tumorzellen in der Leber ähnlich waren (39,78 % und 28,77 %). Positive Korrelationen wurden beim HS für CD86 und Caspase-3 sowie bei beiden Tumoren für Survivin und Ki-67 und PD-L1 und Ki-67 gefunden. Weiterhin wurde in beiden Tumoren MX1 sowohl auf Protein als auch auf mRNS Ebene nachgewiesen.
Schlussfolgerungen: Die vorliegenden Studien zeigen, dass CD80 und CD86 einen Einfluss auf das biologische Verhalten kaniner histiozytärer Tumoren haben. So ist für CD80 eine Rolle bei der Immunevasion und damit eine verringerte zelluläre Immunreaktion anzunehmen, während CD86 einen immunstimulatorischen Effekt vermittelt. Dies ermöglicht potentiell sowohl translationale als auch therapeutische Ansätze. Der Nachweis von MX1 als Molekül der antiviralen Immunantwort in beiden Tumoren deutet auf eine diversere Rolle dieses Proteins bei kaninen Tumoren hin als bisher bekannt.:Inhaltsverzeichnis I
Abkürzungsverzeichnis III
1. Einleitung 1
2. Literaturübersicht 3
2.1 Charakteristika von Krebserkrankungen 3
2.1.1 Allgemeines 3
2.1.2 Evasion der Apoptose 3
2.1.3 Endlose Replikation 5
2.2 Histiozytäre Neoplasien 6
2.2.1 Allgemeines 6
2.2.2 Histiozytäre Erkrankungen beim Hund 7
2.2.3 Histiozytäre Neoplasien bei Katze und Mensch 9
2.3. Immunkontrollpunkte 11
2.3.1 Allgemeines 11
2.3.2 PD-1/PD-L1 und PD-L2 12
2.3.3 CTLA-4/CD80 und CD86 12
2.3.4 LAG-3/CD4, MHC-II und Galectin-3 13
2.3.5 TIM-3/Galectin-9 13
2.3.6 OX40/OX40L 14
2.3.7 Therapeutischer Nutzen 14
2.4 Interferon-Typ-I-Signalweg 17
2.4.1 Allgemeines 17
2.4.2 Besonderheiten des Interferon-Typ-I-Signalweges 19
2.4.3 Bedeutung in der Therapie 20
2.5 Hypothesen 21
3. Publikationen 23
3.1. Publikation 1 23
3.2. Publikation 2 25
4. Diskussion 27
4.1 Einleitung 27
4.2 Effekte auf den Zellzyklus 27
4.3 Potentielle Rolle der untersuchten Immunkontrollpunkte beim biologischen Verhalten 29
4.4 Einfluss der Interferon-vermittelten Immunantwort 30
4.5 Translationale Aspekte der Studienergebnisse 31
4.6 Fazit 32
5. Zusammenfassung 35
6. Summary 37
7. Literaturverzeichnis 39
8. Danksagung 5
Protein Evaluation of Feedstuffs for Horses
No full textThe German Society of Nutrition Physiology has proposed a new protein evaluation system
for horse feeds to estimate pre-cecally digestible crude protein (pcdCP) and amino acids (pcdAA) from
chemical properties. A total of 71 feeds for horses were chemically tested and evaluated according
to the new protein evaluation system. A feeding trial with eight horses tested whether differences
in estimated pcdAA and neutral detergent soluble CP (NDSCP) in the diet were reflected by post-
prandial (ppr) kinetics of plasma lysine (Lys) by feeding a complementary feed (control = CTRL) with
1.02 g Lys/100 kg body weight (BW) as well as three diets with 3.02 g Lys/100 kg BW, as follows:
(i) CTRL with synthetic AA (CTRL + synAA); (ii) CTRL with soybean meal (CTRL + SBM); and (iii)
lucerne pellets (LUC). In comparison to CTRL, the areas of curves (AUCs) of ppr plasma Lys differed:
CTRL < CTRL + SBM (p < 0.01) < CTRL + synAA (p < 0.05). For 71 feeds, the estimated pcdCP was
correlated with the CP content (p < 0.001), NDSCP (p < 0.001), and ash-free neutral detergent fiber
(p < 0.001). A mean neutral detergent insoluble CP content of at least 3–5% can be assumed in horse
feed. It is speculated that the predicted availability of Lys from LUC seems to be underestimated
by the new protein evaluating system. The influence of chewing and microbiota in vivo needs to be
considered in horses
Schilddrüsenhormone und Zinkfingerprotein 423 in der Regulation der Plastizität des weißen Fettgewebes: Dissertation zur Erlangung des akademischen Grades Dr. rer. nat.
No full textSchilddrüsenhormone (SDH) sind wichtige Regulatoren im Fettgewebe, z.B. für den Lipidstoffwechsel und die adaptive Thermogenese. In Nagetieren führt die Applikation von SDH zum „Browning“ im weißen Fettgewebe, also der Rekrutierung beiger Adipozyten, die das Uncoupling Protein 1 exprimieren. Eine frühere Studie der Arbeitsgruppe zeigte, dass die Expression des Zinkfingerprotein 423 (ZFP423) im Fettgewebe von Mäusen in Abhängigkeit des SDH-Status differentiell exprimiert wird. ZFP423 ist ein Transkriptionsfaktor mit dualer Funktion: einerseits initiiert es die Bildung von Adipozyten, andererseits inhibiert es das thermogene Genprogramm und determiniert so einen energiespeichernden weißen Phänotyp. In dieser Dissertation wurde untersucht, ob SDH die Zfp423-Expression im Fettgewebe direkt regulieren und vermittelt durch ZFP423 den funktionalen Adipozytenphänotyp modulieren. Untersucht wurden dabei (I) die molekularen Mechanismen der Regulation des Zfp423-Gens durch SDH, (II) die Bedeutung von SDH für die ZFP423-vermittelte Adipogenese und (III) die thermogene Aktivität beiger Adipozyten, (IV) die kooperativen Mechanismen der thermogenen Regulation von weißem Fettgewebe durch ZFP423 und SDH-Rezeptor β sowie (V) die Relevanz von SDH und ZNF423 im humanen Fettgewebe.:1. Einführung
2. Zielsetzung
3. Publikationen
4. Zusammenfassung der Arbeit
5. Literaturverzeichnis
6. Anlage