Experimental studies on population genetics of complement 3 (C3) and serum component transferin (Tf) in the population of Northern Bavaria]

Within a population sample concerning 2500 blood donors of Northern Bavaria, the population genetics of the Systems C3 and Tf have been investigated. The calculated gene frequencies are: C3S = 0,789; C3F = 0,2028; C3Var. = 0,0082; TfC = 0,9960; TfVar. = 0,0040. As a "new" variant C3F1,55 has been found.     

Toxin-Independent Virulence of Bacillus anthracis in Rabbits

The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play a major role in pathogenicity. In the guinea pig (GP) model we have previously shown that deletion of all three toxin components results in a relatively moderate attenuation in virulence, indicating that B. anthracis possesses an additional toxin-independent virulence mechanism. To characterize this toxin-independent mechanism in anthrax disease, we developed a new rabbit model by intravenous injection (IV) of B. anthracis encapsulated vegetative cells, artificially creating bacteremia. Using this model we were able to demonstrate that also in rabbits, B. anthracis mutants lacking the toxins are capable of killing the host within 24 hours. This virulent trait depends on the activity of AtxA in the presence of pXO2, as, in the absence of the toxin genes, deletion of either component abolishes virulence. Furthermore, this IV virulence depends mainly on AtxA rather than the whole pXO1. A similar pattern was shown in the GP model using subcutaneous (SC) administration of spores of the mutant strains, demonstrating the generality of the phenomenon. The virulent strains showed higher bacteremia levels and more efficient tissue dissemination; however our interpretation is that tissue dissemination per se is not the main determinant of virulence whose exact nature requires further elucidation.     

Characterization of extremely halophilic Archaea isolated from the Ayvalik Saltern,Turkey

Seven extremely halophilic strains were isolated from the Ayvalik Saltern in the north-eastern part of Turkey. Chemical analyses of the brine and salt samples were performed to measure their salt content, hardness and pH. Isolated strains were tested for their antibiotic sensitivities; cell and colony morphologies; hydrolysis of casein, starch, gelatin, Tween 20 and Tween 80; and oxidase and catalase activity. All strains were found to belong to the domain Archaea. Characterization of polar lipids by thin layer chromatography indicated that all isolates contained phytanyl diether derivatives of phosphatidylglycerol (PG), the methyl ester of phosphatidyl glycerophosphate (PGP-Me), and phosphatidylglycerosulphate (PGS). Four isolates had triglycosyl diether (TGD-2) as glycolipid, and the other three contained a sulphated diglycosyl diether instead. All isolates were examined for the presence of plasmids by agarose gel electrophoresis. Four strains were found to harbour plasmids ranging in size from 13.8 to 15.3 kbp. Correlation between the protein profiles in SDS–PAGE and the phenotypic properties of the strains was poor. The data presented here provide the first published account of the microbiota of the Ayvalik saltern, which provides a large part of the salt produced in Turkey.     

The Arabidopsis STRESS RESPONSE SUPPRESSOR DEAD‐box RNA helicases are nucleolar‐ and chromocenter‐localized proteins that undergo stress‐mediated relocalization and are involved in epigenetic gene silencing

DEAD‐box RNA helicases are involved in many aspects of RNA metabolism and in diverse biological processes in plants. Arabidopsis thaliana mutants of two DEAD‐box RNA helicases, STRESS RESPONSE SUPPRESSOR1 (STRS1) and STRS2 were previously shown to exhibit tolerance to abiotic stresses and up‐regulated stress‐responsive gene expression. Here, we show that Arabidopsis STRS‐overexpressing lines displayed a less tolerant phenotype and reduced expression of stress‐induced genes confirming the STRSs as attenuators of Arabidopsis stress responses. GFP–STRS fusion proteins exhibited localization to the nucleolus, nucleoplasm and chromocenters and exhibited relocalization in response to abscisic acid (ABA) treatment and various stresses. This relocalization was reversed when stress treatments were removed. The STRS proteins displayed mis‐localization in specific gene‐silencing mutants and exhibited RNA‐dependent ATPase and RNA‐unwinding activities. In particular, STRS2 showed mis‐localization in three out of four mutants of the RNA‐directed DNA methylation (RdDM) pathway while STRS1 was mis‐localized in the hd2c mutant that is defective in histone deacetylase activity. Furthermore, heterochromatic RdDM target loci displayed reduced DNA methylation and increased expression in the strs mutants. Taken together, our findings suggest that the STRS proteins are involved in epigenetic silencing of gene expression to bring about suppression of the Arabidopsis stress response.     

Computational and experimental analysis of drug binding to the Influenza M2 channel

The Influenza Matrix 2 (M2) protein is the target of Amantadine and Rimantadine which block its H⁺ channel activity. However, the potential of these aminoadamantyls to serve as anti-flu agents is marred by the rapid resistance that the virus develops against them. Herein, using a cell based assay that we developed, we identify two new aminoadamantyl derivatives that show increased activity against otherwise resistant M2 variants. In order to understand the distinguishing binding patterns of the different blockers, we computed the potential of mean force of the drug binding process. The results reveal that the new derivatives are less mobile and bind to a larger pocket in the channel. Finally, such analyses may prove useful in designing new, more effective M2 blockers as a means of curbing influenza. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.     

Effects of Chronic Arginase Inhibition with Norvaline on Tau Pathology and Brain Glucose Metabolism in Alzheimer's Disease Mice

Neurochemical Research - Alzheimer's disease (AD) is an insidious neurodegenerative disorder representing a serious continuously escalating medico-social problem. The AD-associated progressive...     

Cancellous and cortical morselized allograft in revision total hip replacement: A biomechanical study of implant stability

To restore femoral intramedullary bone stock loss in revision surgery of failed total hip arthroplasties, impacted morselized cancellous allograft is recommended. This study investigated the mechanical properties of both impacted cortical (group A) and cancellous (group B) morselized bone graft for reconstruction of femoral bones. Ten matched pairs of fresh frozen human femora were prepared by over-reaming to create a smooth-walled cortical shell. Each pair had one cortical and one cancellous impacted morselized allograft and cement. Stem subsidence was evaluated by a cyclic axial load, which was applied by a servohydraulic test. The stem subsidence was measured for initial subsidence (subsidence at the first 1000 cycles), the total axial subsidence (subsidence at the end of cycles under load) and the final axial subsidence (subsidence after the unloading phase). Torque test was measured by torsional loads through the prosthetic femoral heads. Total axial subsidence was significantly higher in group B (mean: 1.32+/-0.32 mm) compared to group A (mean: 0.94+/-0.26 mm) (P<0.01).There was no significant difference between the two groups in terms of initial subsidence (P=0.09) and final axial subsidence.The mean maximum torque before failure was 39.5+/-22.2 N-m for the cortical morselized allograft and 32.5+/-18.1N-m for cancellous.We concluded that impacted morselized cortical bone graft used for reconstruction of contained femoral bone loss in revision hip arthroplasty, may reduce the stem subsidence. Further animal experimentation for mechanical and histological evaluation of in vivo application is warranted.     

Delayed puberty and hypoplastic uterus associated with hyperprolactinemia: successful treatment with bromocriptine

A 15-year-old girl referred because of primary amenorrhea was found to have a hypoplastic uterus and persistent hyperprolactinemia (72-110 ng/ml). The gonadotrophin-dependent pubertal signs, i.e. breast and vulvar development, were significantly retarded (Tanner stage 2-3) while sexual hair was well developed; bone age was 13 years. The endocrinological evaluation revealed gonadotrophin secretion (LH-basal: 0.85-1.25; peak after LH-RH: 10.4 mIU/ml; FSH-basal: 1.63-2.5; peak: 8.2 mIU/ml) and E2 levels (26-68 pg/ml) which were appropriate for Tanner stage 3. The high basal levels of PRL were nonresponsive to either stimulatory (TRH) or inhibitory (nomifensine) agents. CT scan of the brain suggested the presence of a pituitary microadenoma. Following therapy with bromocriptine (2.5 mg/day) plasma PRL levels dropped to normal (5-6.8 ng/ml) with an accompanying catch-up of pubertal development and linear growth and a marked increase in size of the uterus as documented by repeated ultrasonographic examinations. Menarche occurred 5 months after initiation of therapy, followed by regular menses thereafter. Repeated CT scan of the brain showed a decrease in the density and size of the still persisting lesion. This patient demonstrates that hyperprolactinemia can cause delayed puberty with a particular inhibitory effect on uterine growth and development.     

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation: Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.