Transgenic mouse models of angiotensin receptor subtype function in the cardiovascular system

Angiotensin II mediates is biological actions via different subtypes of G protein-coupled receptors, termed AT(1) and AT(2) receptors. In rodents, two AT(1) receptors have been identified, AT(1A) and AT(1B), whereas in humans a single AT(1) receptor exists. Recently, a number of transgenic animal models have been generated which overexpress or lack functional angiotensin II receptor subtypes. This review focuses on the physiological significance of angiotensin II receptor subtype diversity in the cardiovascular system. In the mouse, AT(1A) receptors are the major regulators of cardiovascular homeostasis by determining vascular tone and natriuresis. In addition, AT(1A) receptors mediate growth-stimulating signals in vascular and cardiac myocytes. AT(1B) receptors participate in blood pressure regulation, and their functions become apparent when the AT(1A) receptor gene is deleted. Deletion of the mouse gene for the AT(2) receptor subtype led to hypersensitivity to pressor and antinatriuretic effects of angiotensin II in vivo, suggesting that the AT(2) receptor subtype counteracts some of the biological effects of AT(1) receptor signalling.     

Comparative genomic analysis reveals significant enrichment of mobile genetic elements and genes encoding surface structure-proteins in hospital-associated clonal complex 2 Enterococcus faecalis

Background  

Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40).     

Lipid-Lowering Effects of Tetradecylthioacetic Acid in Antipsychotic-Exposed,Female Rats: Challenges with Long-Term Treatment

Background

Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain.

Aims

In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid.

Methods

Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated.

Results

The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics.

Conclusion

TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a more valid long-term rat model for antipsychotic-induced metabolic adverse effects is required.     

Expression and characterization of human glycosylated interleukin-1 receptor antagonist in Pichia pastoris

Interleukin-1 receptor antagonist is an inhibitor of the pro-inflammatory action of interleukin-1. The gene encoding for interleukin-1 receptor antagonist (IL-1ra) was cloned into a Pichia pastoris expression vector pPICzalphaA (Invitrogen, USA) and transformed into P. pastoris strain SMD1168H. Multi-copy selection of the gene produced a high expressing strain of IL-1ra that produced 17mg/L of total secreted purified protein. The IL-1ra produced in P. pastoris was a mixture of glycosylated and non-glycosylated IL-1ra where 70% of the total protein was glycosylated. SP-Sepharose purification allowed for separation of the two expressed forms of IL-1ra, which permits biochemical investigation of glycosylated and non-glycosylated IL-1ra using one expression system. Mass spectrometric analysis revealed the expression of the full-length protein and that the glycosylated IL-1ra contained high mannose glycoforms that ranged from Man(9)GlcNAc(2) to Man(14)GlcNAc(2).     

Translocation patterns in xanthium in relation to long day inhibition of flowering

The nature of long day inhibition of flowering in the short day plant Xanthium strumarium L. was studied by correlating the flowering response with the translocation of ¹⁴C-assimilates from induced leaves or parts thereof to the shoot tips.     

Influence of mitotic delay on the results of biological dosimetry for high doses of ionizing radiation

The purpose of this study was to systematically investigate how high doses of sparsely and densely ionizing radiations influence the proliferation time of lymphocytes in short-term cultures and, consequently, the observed frequencies of dicentric and centric ring chromosomes. Peripheral blood samples from five volunteers were irradiated with high doses of 200 kV X-rays and with neutrons with a mean energy of <E _n>=2.1 MeV. First division metaphase cells were collected after different culture times of 48, 56, and 72 h and dicentrics, centric ring chromosomes, and acentric fragments were determined. The data hint at considerable mitotic delay. The main increase in the number of chromosome aberrations occurred between 48 and 72 h after an X-ray exposure and between 56 and 72 h after neutron exposure. When the data were used for a calibration of aberration frequency versus dose, subsequent dose estimations resulted, however, in comparable values. Thus, in spite of the influence of mitotic delay on observable chromosome aberrations, at least for the radiation types investigated here, a culture time of 48 h is acceptable for biological dosimetry.     

Contrasting population structures in two sympatric anurans: implications for species conservation

A general prediction of the neutral theory of evolution is that genetic diversity should correlate positively with effective population size. We show here that diversity across eight microsatellite loci was consistently and substantially lower in one common amphibian (Bufo bufo) than in another with similar life history traits (Rana temporaria) despite B. bufo having the larger breeding assemblage sizes. However, B. bufo breeding assemblages were much more highly differentiated than those of R. temporaria according to both Fst and Rst estimators. These differences occurred in shared habitats across identical geographical distances. The patterns of genetic diversity and differentiation detected in these two species were probably a consequence of high gene flow in R. temporaria but much lower gene flow among the larger but more dispersed B. bufo assemblages. These observations highlight the difficulty of defining the boundaries of wild populations, and show how two broadly similar species can exhibit very different population dynamics.     

DNA‐Barcoding. Taxonomie des 21. Jahrhunderts

Das internationale “Consortium for the Barcode of Life” will ein standardisiertes DNA‐Fragment aller Organismenarten der Welt sequenzieren. Dieser “Barcode” soll dazu dienen, Arten schnell und eindeutig zu bestimmen. Ziel ist neben der Katalogisierung des Lebens auf unserem Planeten auch die Entwicklung eines handlichen Geräts, das in der Lage ist, kostengünstig kleine Proben eines Organismus einer Art zuzuordnen. Profitieren können von diesem Ansatz nicht nur die Grundlagenforschung, sondern auch gesellschaftliche und politische Institutionen. Zudem stellt DNA‐Barcoding einen sehr wichtigen Beitrag zur Beschreibung der Artenvielfalt dar, da es diesen Prozess stark beschleunigen kann.