Central nervous system actions of growth hormone on brain monoamine levels and behavior of juvenile rainbow trout

Growth hormone (GH) has been demonstrated to alter the behavior of juvenile salmonids. However, the mechanisms behind this action are not yet understood. In mammals and birds, peripheral GH treatment has been shown to affect monoaminergic activity in the central nervous system, which may be a mechanism whereby GH alters behavior. To investigate if GH may influence behavior directly at the central nervous system, juvenile rainbow trout were injected with GH into the third ventricle of the brain, whereupon physical activity and food intake were observed during 2 h. Thereafter, brains were sampled and the content of serotonin, dopamine, and noradrenaline and their metabolites were measured in hypothalamus, telencephalon, optic tectum, and brainstem. The GH-treated fish increased their swimming activity relative to sham-injected controls, while appetite remained unchanged, compared with sham-injected controls. Analysis of brain content of monoamines revealed that the GH treatment caused a decrease in the dopamine metabolite homovanillic acid in the hypothalamus, indicating a lowered dopaminergic activity. It is concluded that GH may alter behavior by acting directly on the central nervous system in juvenile rainbow trout. Furthermore, GH seems to alter the dopaminergic activity in the hypothalamus. Whether this is a mechanism whereby GH affects swimming activity remains to be clarified.     

Neural Correlates of Emotional Interference in Social Anxiety Disorder

Disorder-relevant but task-unrelated stimuli impair cognitive performance in social anxiety disorder (SAD); however, time course and neural correlates of emotional interference are unknown. The present study investigated time course and neural basis of emotional interference in SAD using event-related functional magnetic resonance imaging (fMRI). Patients with SAD and healthy controls performed an emotional stroop task which allowed examining interference effects on the current and the succeeding trial. Reaction time data showed an emotional interference effect in the current trial, but not the succeeding trial, specifically in SAD. FMRI data showed greater activation in the left amygdala, bilateral insula, medial prefrontal cortex (mPFC), dorsal anterior cingulate cortex (ACC), and left opercular part of the inferior frontal gyrus during emotional interference of the current trial in SAD patients. Furthermore, we found a positive correlation between patients’ interference scores and activation in the mPFC, dorsal ACC and left angular/supramarginal gyrus. Taken together, results indicate a network of brain regions comprising amygdala, insula, mPFC, ACC, and areas strongly involved in language processing during the processing of task-unrelated threat in SAD. However, specifically the activation in mPFC, dorsal ACC, and left angular/supramarginal gyrus is associated with the strength of the interference effect, suggesting a cognitive network model of attentional bias in SAD. This probably comprises exceeded allocation of attentional resources to disorder-related information of the presented stimuli and increased self-referential and semantic processing of threat words in SAD.     

The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD)

Apolipoprotein B (apoB) is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis. The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum (ER) and is mediated by the proteasome. To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system. We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation. However, the Ssb Hsp70 chaperones have no effect on apoB turnover. To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed. This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation (ERAD), establishes a role for Sse1/Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol.     

Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains

Escherichia coli is the most common organism associated with asymptomatic bacteriuria (ABU) in humans. In contrast to uropathogenic E. coli (UPEC) that cause symptomatic urinary tract infection, very little is known about the mechanisms by which these strains colonize the urinary tract. Here, we have investigated the biofilm-forming capacity on abiotic surfaces of groups of ABU strains and UPEC strains in human urine. We found that there is a strong bias; ABU strains were significantly better biofilm formers than UPEC strains. Our data suggest that biofilm formation in urinary tract infectious E. coli seems to be associated with ABU strains and appears to be an important strategy used by these strains for persistence in this high-flow environment.     

The ways of realization of high specificity and efficiency of enteropeptidase

Comparative substrate analysis of full-length bovine enteropeptidase and trypsin, bovine and human enteropeptidase light chains was performed using model N-terminal dodecapeptides corresponding to wild-type human trypsinogen and pancreatitis-associated mutant trypsinogens K23R and D22G. The substitution of Lys residue by Arg at P1 leads to 2-fold increase in the efficiency of enteropeptidase hydrolysis; the absence of the negatively charged residue at P2 reduces the efficiency of such hydrolysis by two orders of magnitude. The difference in efficiency of peptide chain hydrolysis after Lys/Arg residues by enteropeptidase compared to trypsin is equal to the difference in hydrolysis by serine proteases of different primary specificity of their specific substrates.     

Magnetic fluorescent microparticles as markers for particle transfer in extracorporeal blood purification

The microspheres-based detoxification system (MDS) is a combined membrane-adsorption system for extracorporeal blood purification in which adsorbent microparticles are recirculated in an extracorporeal filtrate circuit. Because the plasma filter represents the only barrier between the adsorbents and the patient's blood, there is the potential risk of particle entrance into the patient in case of a membrane rupture. To guarantee first fault safety of the system required for clinical application, magnetic fluorescent microparticles are added as markers to the adsorbent circuit. Detection of these particles in the venous blood line results in immediate shutdown of the pumps. Magnetic beads were functionalized with cresyl violet and tested with an in vitro setup of the particle detector to assess the detection limit in different matrices (water versus blood) as well as the influence of flow rate and particle size on the signal. In addition, biocompatibility and influence of sterilization on the performance of the particles were assessed. Functionalization of the magnetic particles with cresyl violet yielded fluorescent particles that were stable at 4 degrees C for at least 12 months. No leakage of dye was detectable, and the particles were neither cytotoxic nor mutagenic. The particles could be steam sterilized without significant loss in fluorescence intensity. With an in vitro setup of the particle detector, 0.1 mg and 5 mg of particles were reproducibly detectable in water and blood, respectively.