Differentially Expressed Gene Patterns in Ascarid-Infected Chickens of Higher- or Lower-Performing Genotypes

Here, we describe the first transcriptomic investigation of the peripheral blood of chickens exposed to Ascaridia galli and Heterakis gallinarum infections. We investigated differentially expressed gene (DEG) patterns in two chicken genotypes with either a higher (Lohmann Brown Plus, LB) or lower (Lohmann Dual, LD) laying performance level. The hens were experimentally coinfected with A. galli and H. gallinarum, and their worm burdens and infection parameters were determined six weeks post infection. Based on most representative infection parameters, the hens were clustered into lower- and higher-infection intensity classes. We identified a total of 78 DEGs contributing to infection-related phenotypic variation in the two genotypes. Our data showed significant upregulation of Guanylate Binding Protein 7 (GBP7) in LD hens, making it a promising candidate for tolerance to ascarid infections in chickens. Gene ontology analysis revealed higher transcriptome activity related to biological processes such as "response to external stimulus" in LB hens, implying a higher stress response in this genotype. In contrast, LD hens showed higher transcriptomic expression of genes related to ontology classes that are possibly associated with a higher tolerance to infections. These findings may help explain why lower-performing genotypes (i.e., LD) are less sensitive to infections in terms of maintaining their performance

Validation of commercially available ELISAs for the detection of circulating sclerostin in hemodialysis patients

ABSTRACT BACKGROUND: Sclerostin is an endocrine regulator in chronic kidney disease -mineral and bone disorder (CKD-MBD). Validation of assay comparability and pre-analytical handling is mandatory for establishment of sclerostin as a biomarker

Correlation of the measurement of incisor inclination in dental casts and in lateral cephalometric radiographs

Anhand von 75 seitlichen Fernröntgenaufnahmen und korrespondierenden Gipsmodellen wurde untersucht, ob die konventionell am FRS gewonnenen Werte der Frontzahninklinationswinkel im Ober- und Unterkiefer und des Interinzisalwinkels aus am Modell bestimmten Werten berechnet werden können. Nach der Modellduplikation erfolgte die Entfernung der linken Seite durch Trimmen. Durch den höchsten Punkt der Inzisalkante und die Hälfte der labio-oralen Distanz, gemessen zwischen den tiefsten Punkten des Sulkus, wurde eine Gerade auf die zur Kauebene parallelen jeweiligen Sockelebenen gezogen, der dorsale Winkel gemessen und mit entsprechenden Messwerten aus dem FRS verglichen. In einem weiteren Schritt wurden in Analogie der Messungen am Modell die Frontzahninklinationen auf eine am FRS neu eingeführte Kauebene bezogen. In einer Vorauswertung wurden diese Messmethoden als reproduzierbar und wiederholbar bestätigt. Die mit Hilfe einer linearen Regression untersuchte Vorhersagbarkeit der am FRS ermittelten Werte für die Frontzahninklinationswinkel im Ober- und Unterkiefer (R² = 0,33 / 0,54) und den Interinzisalwinkel (R² = 0,73) aus am Modell bestimmten Werten erreichte nicht die klinisch erforderliche Präzision. Am FRS konnte im Vergleich zu den konventionell verwendeten Bezugsebenen durch die Messung der Frontzahninklinationswinkel zur Kauebene die Güte der Vorhersagbarkeit aus am Modell ermittelten Werten gesteigert werden (R² = 0,53 / 0,74). Eine Auswertung nach Angle Klasse, skelettaler Klasse, Wachstumsmuster, Overjet, Overbite und dem Verhältnis des Zahnmaterials beider Kiefer ergab keine wesentliche Verbesserung der Vorhersagbarkeit. Das Gipsmodell kann derzeit das FRS als diagnostische Grundlage zur Bestimmung betreffender Winkel nicht ersetzen. Methodische Unterschiede der am FRS und am Modell untersuchten Messtechniken und auf beiden Seiten bestehende Fehlerquellen erschweren einen Vergleich der Messungen. Zukünftig erscheint es denkbar, durch eine computergestützte Bestimmung der Winkel anhand von digitalisierten Gipsmodellen die Präzision der Methode zu erhöhen.A total of 75 lateral cephalometric radiographs and corresponding dental casts were evaluated to determine if radiographic measurements of the incisor inclination and the interincisal angle can be calculated from dental casts. The dental casts were duplicated and the left sides of the copies were trimmed off. A line was drawn from the highest point of the incisal edge to the half-way point between the labial and the oral gingival sulcus. The dorsal angle formed by this line and the base of the cast parallel to the occlusal plane was then compared to the corresponding values from cephalometric radiographs. The incisor inclinations were then compared to a newly introduced occlusion plane in the cephalometric radiographs as in the measurements of the dental casts. A preliminary evaluation had shown these measurement methods to be reproducible and repeatable. Linear regression analysis was used to establish the predictability of the cephalometric radiographs values from those based on dental casts. This analysis showed that the predictability of measurements of the upper and lower central incisor inclination (R² = 0.33 / 0.54) and of the interincisal angle (R² = 0.73) was not sufficiently accurate for clinical application. While predictability could be increased by determining the incisor inclination in relation to an occlusal plane in the cephalometric radiograph (R² = 0.53 / 0.74), it was not enhanced by evaluation of Angle class, skeletal class, growth pattern, overjet, overbite or the relation of the tooth size of both jaws. It can thus be concluded that dental casts cannot presently be used in place of lateral cephalometric radiograph as a diagnostic tool for the determination of the angles in question. Methodical differences in measurement techniques and other sources of error also complicate the comparison of the two methods. However, it is conceivable that the accuracy of this method can be enhanced in future by computer-aided evaluation of the angles in digitalized dental casts

Complement Activation-Related Pathophysiological Changes in Anesthetized Rats: Activator-Dependent Variations of Symptoms and Mediators of Pseudoallergy

Complement (C) activation can underlie the infusion reactions to liposomes and other nanoparticle-based medicines, a hypersensitivity syndrome that can be partially reproduced in animal models. However, the sensitivities and manifestations substantially differ in different species, and C activation may not be the only cause of pathophysiological changes. In order to map the species variation of C-dependent and -independent pseudoallergy (CARPA/CIPA), here we used known C activators and C activator liposomes to compare their acute hemodynamic, hematological, and biochemical effects in rats. These C activators were cobra venom factor (CVF), zymosan, AmBisome (at 2 doses), its amphotericin B-free vehicle (AmBisombo), and a PEGylated cholesterol-containing liposome (PEG-2000-chol), all having different powers to activate C in rat blood. The pathophysiological endpoints measured were blood pressure, leukocyte and platelet counts, and plasma thromboxane B2, while C activation was assessed by C3 consumption using the Pan-Specific C3 assay. The results showed strong linear correlation between C activation and systemic hypotension, pointing to a causal role of C activation in the hemodynamic changes. The observed thrombocytopenia and leukopenia followed by leukocytosis also correlated with C3 conversion in case of C activators, but not necessarily with C activation by liposomes. These findings are consistent with the double hit hypothesis of hypersensitivity reactions (HSRs), inasmuch as strong C activation can fully account for all symptoms of HSRs, but in case of no-, or weak C activators, the pathophysiological response, if any, is likely to involve other activation pathways

Validation of commercially available ELISAs for the detection of circulating sclerostin in hemodialysis patients

Sclerostin is an endocrine regulator in chronic kidney disease - mineral and bone disorder (CKD-MBD). Validation of assay comparability and pre-analytical handling is mandatory for establishment of sclerostin as a biomarker.status: publishe

Does hepatotoxicity interfere with endocrine activity in zebrafish (Danio rerio)?

Vitellogenin (VTG), a well-established biomarker for the diagnosis of endocrine activity in fish, is used in multiple OECD test guidelines (TG) to identify activities of chemicals on hormonal pathways. However, the synthesis of VTG may not only be modified by typical endocrine-related pathways, but also through non-endocrine-mediated processes. In particular, hepatotoxicity, i.e. toxicant-induced impairment of liver structure and function, might influence VTG as a biomarker, since VTG is synthesized in hepatocytes. An intimate understanding of the interplay between endocrine-related and non-endocrine-related pathways influencing VTG production is crucial for the avoidance of erroneous diagnoses in hazard assessment for regulatory purposes of chemical compounds. In order to investigate whether hepatotoxicity may interfere with hepatic VTG synthesis, adult zebrafish (Danio rerio) were exposed to three well-known hepatotoxicants, acetaminophen, isoniazid and acetylsalicylic acid, according to OECD TG 230. Various hepatotoxicity- and endocrine system-related endpoints were recorded: mRNA expression of selected endocrine- and hepatotoxicity-related marker genes in the liver; VTG levels in head/tail homogenates; and liver histopathology. All three test compounds induced significant, but mild single cell necrosis of hepatocytes and transcriptional changes of hepatotoxicity-related marker genes, thus confirming hepatotoxic effects. A positive correlation between hepatotoxicity and reduced hepatic VTG synthesis was not observed, with the single exception of a weak increase in female zebrafish exposed to APAP. This suggests that - in studies conducted according to OECD TG 229 or 230 - it is unlikely that hepatotoxic chemicals will interfere with the hepatic capacity for VTG synthesis

The Constitution and Conflict-of-Laws Treaties: Upgrading the International Comity

Relationships between worm burdens and infection proxies based on pooled data. Linear relationships between worm burdens with plasma antibody, egg yolk antibody and faecal egg counts in chickens experimentally infected (red dot) with Ascaridia galli or with Heterakis gallinarum and uninfected control birds (green dot). Note that the correlations are based on pooled data from infected and uninfected controls within each nematode infection. (TIF 161 kb