The atrial natriuretic peptide and guanylyl cyclase-A system modulates pancreatic beta-cell function

Atrial natriuretic peptide (ANP) and its guanylyl cyclase-A (GC-A) receptor are being involved in metabolism, although their role in the endocrine pancreas is still greatly unknown. The aim of this work is to study a possible role for the ANP/GC-A system in modulating pancreatic beta-cell function. The results presented here show a direct effect of the GC-A receptor in regulating glucose-stimulated insulin secretion (GSIS) and beta-cell mass. GC-A activation by its natural ligand, ANP, rapidly blocked ATP-dependent potassium (K(ATP)) channel activity, increased glucose-elicited Ca(2+) signals, and enhanced GSIS in islets of Langerhans. The effect in GSIS was inhibited in islets from GC-A knockout (KO) mice. Pancreatic islets from GC-A KO mice responded to increasing glucose concentrations with enhanced insulin secretion compared with wild type (WT). Remarkably, islets from GC-A KO mice were smaller, presented lower beta-cell mass and decreased insulin content. However, glucose-induced Ca(2+) response was more vigorous in GC-A KO islets, and basal K(ATP) channel activity in GC-A KO beta-cells was greatly diminished compared with WT. When protein levels of the two K(ATP) channel constitutive subunits sulfonylurea receptor 1 and Inward rectifier potassium channel 6.2 were measured, both were diminished in GC-A KO islets. These alterations on beta-cell function were not associated with disruption of glucose tolerance or insulin sensitivity in vivo. Glucose and insulin tolerance tests were similar in WT and GC-A KO mice. Our data suggest that the ANP/GC-A system may have a modulating effect on beta-cell function

Gewaltschutz im Gesundheitsbereich : Die ärztliche Schweigepflicht im Berufsrecht als Rechtsvergleich Österreich - Deutschland

In der heutigen Zeit leiden europaweit und auf der ganzen Welt immer noch viele Frauen und Kinder unter Gewalt im familiären Bereich. Auch Männer sind davon betroffen, jedoch in einem verhältnismäßig geringen Ausmaß. Diese Arbeit beschäftigt sich zu Beginn mit dem Begriff und den Folgen von Partnerschaftsgewalt. Des Weiteren wird auf ausgewählte nationale, europarechtliche und völkerrechtliche Bestimmungen zum Thema „Häusliche Gewalt‘“ eingegangen. Die immense Bedeutung des Gesundheitswesens, welches oftmals die erste und einzige Anlaufstelle für Opfer von familiärer Gewalt ist, wird durchleuchtet. Spezielle Schulungen sollen Ärzte und den gesamten Gesundheitsbereich in Bezug auf diese Angelegenheit sensibilisieren. Danach wird die ärztliche Schweigepflicht einerseits und die ärztliche Anzeigepflicht andererseits behandelt, worin sich ein Spannungsverhältnis ergeben kann sowie deren Durchbrechungen in berufsrechtlicher und in strafrechtlicher Hinsicht werden beschrieben. Die große Bedeutung der ärztlichen Dokumentationspflicht wird aufgezeigt und Sanktionen werden erläutert, wenn der Arzt die Schweige-, Anzeige- bzw. die Dokumentationspflicht verletzt. Zuletzt werden zwei aktuelle Projektbeispiele vorgestellt, welche zeigen sollen, welche Bedeutung die Dokumentationspflicht in der Praxis hat und wie wichtig es für Opfer von häuslicher Gewalt ist, sich zeitnah untersuchen zu lassen, um Beweise für allfällige spätere Gerichtsverfahren im Falle einer Anzeigeerstattung zu sichern. In allen Kapiteln wird die deutsche sowie die österreichische Rechtslage ergründet.eingereicht von Birgit GassnerUniversität Linz, Diplomarbeit, 2018(VLID)283645

Impact of Extracellular Acidity on the Activity of P-glycoprotein and the Cytotoxicity of Chemotherapeutic Drugs

The expression and activity of P-glycoprotein (pGP) play a role in the multidrug resistance of tumors. Because solid-growing tumors often show pronounced hypoxia or extracellular acidosis, this study attempted to analyze the impact of an acidic environment on the expression and activity of pGP and on the cytotoxicity of chemotherapeutic agents. For this, prostate carcinoma cells were exposed to an acidic extracellular environment (pH 6.6) for up to 24 hours. pGP activity was more than doubled after 3 to 6 hours of incubation in acidic medium, whereas cellular pGP expression remained constant, indicating that increased transport rate is the result of functional modulation. In parallel, the cytotoxic efficacy of daunorubicin showed pronounced reduction at low pH, an effect that was reversible on coincubation with a pGP inhibitor. A reduction of intracellular Ca(2+) concentration by 35% under acidic conditions induced a higher transport rate of pGP, an effect comparable to that found on inhibition of protein kinase C (PKC). These data indicate that pGP activity is increased by acidic pH presumably as a result of lowered intracellular calcium levels and inhibition of PKC. These findings may explain the reduced cytotoxicity of chemotherapeutic agents in hypoxic/acidic tumors

Delimitation results of bPTP algorithm

Species delimitation results of the Bayesian Poisson tree processes (bPTP) algorithm. Values on branches are posterior delimitation probabilities

Supplementary_material3_ITS2_alignment

Internal transcribed spacer 2 final alignmen

Data from: Taxonomist’s nightmare … evolutionist’s delight: an integrative approach resolves species limits in jumping bristletails despite widespread hybridization and parthenogenesis

Accurate species delimitation is fundamental to biology. Traditionally, species were delimited based on morphological characters, sometimes leading to taxonomic uncertainty in morphologically conserved taxa. Recently, multiple taxonomically challenging cases have benefited from integrative taxonomy – an approach that highlights congruence among different disciplines and invokes evolutionary explanations for incongruence, acknowledging that different methods can mirror different stages of the speciation continuum. Here, we used a cohesive protocol for integrative taxonomy to revise species limits in 20 nominal species and four morphospecies of an ancestrally wingless insect group, the jumping bristletail genus Machilis from the European Eastern Alps. Even though morphologically conserved, several small-scale endemic species have been described from the Eastern Alps based on variation in hypodermal pigmentation patterns – a highly questionable character. As valuable as these endemics are for conservation, they have never been verified by alternative methods. Using traditional morphometrics, mitochondrial DNA, ribosomal DNA, and amplified fragment-length polymorphism markers, we identify six nominal species as taxonomic junior synonyms (Machilis alpicola Janetschek, 1953 syn. n. under M. vagans Wygodzinsky, 1941; M. ladensis Janetschek, 1950 syn. n., M. robusta Wygodzinsky, 1941 syn. n., and M. vicina Wygodzinsky, 1941 syn. n. under M. inermis Wygodzinsky, 1941; M. aleamaculata Wygodzinsky, 1941 syn n. under M. montana Wygodzinsky 1941; M. pulchra Janetschek 1950 syn. n. under M. helleri Verhoeff 1910) and describe two new species (Machilis cryptoglacialis sp. n. and Machilis albida sp. n.), one uncovered from morphological crypsis and one never sampled before. Building on numerous cases of incongruence among data sources, we further shed light on complex evolutionary histories including hybrid speciation, historical and recent hybridization, and ongoing speciation. We hypothesize that an inherent affinity to hybridization, combined with parallel switches to parthenogenesis and repeated postglacial colonization events may have boosted endemicity in Eastern Alpine Machilis. We thus emphasize the importance of integrative taxonomy for rigorous species delimitation and its implication for evolutionary research and conservation in taxonomically challenging taxa