Contribution of individual retinal ganglion cell responses to velocity and acceleration encoding

We investigate the capability of turtle retinal ganglion cell (RGC) ensembles to simultaneously encode multiple aspects of visual motion: speed, direction, and acceleration of moving patterns. Bayesian stimulus reconstruction reveals that the instantaneous firing rates of RGCs contain information about all of these stimulus properties. Stimulus velocity is mainly encoded by steady-state firing rates, whereas acceleration can be reconstructed from transient components in RGC activity induced by abrupt velocity changes. Therefore neurons in higher brain areas may in principle extract information about changing velocity from the instantaneous firing activity of RGCs, without the need to compare responses to present velocities to previous ones. However, reconstruction requires the estimation of a combined acceleration and velocity signal, indicating that RGC ensembles signal both properties simultaneously. In accordance with this conclusion, combined velocity/acceleration sensitivity enhances the similarity of artificial spike trains to experimental data by 50% compared with the case of pure velocity tuning. Decoding of motion direction in addition to speed and acceleration requires direction-sensitive cells, which generate higher firing rates for one of the motion directions and therefore show asymmetric velocity tuning. By dividing the entire ensemble of simultaneously recorded cells into one group of direction-sensitive cells and one group with symmetric tuning, we demonstrate that the population of direction-sensitive cells encodes a combination of motion speed, acceleration, and direction. However, estimation of velocity and acceleration is improved by including the larger group of RGC responses that are sensitive to speed but not to motion direction.     

Entwicklungen und Herausforderungen der Stillpraxis in den Ländern des südlichen Afrikas

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Da es an der Überlegenheit des Stillens gegenüber anderen Formen der Säuglingsernährung keinen Zweifel mehr...     

Selbsterfahrung in der Psychodrama Ausbildung

Zeitschrift für Psychodrama und Soziometrie - In diesem Beitrag der Zeitschrift für Psychodrama und Soziometrie wird erörtert, dass Selbsterfahrung in der Ausbildung zur...     

Quantitative T2* (T2 star) relaxation times predict site specific proteoglycan content and residual mechanics of the intervertebral disc throughout degeneration

Degeneration alters the biochemical composition of the disc, affecting the mechanical integrity leading to spinal instability. Quantitative T2* MRI probes water mobility within the macromolecular network, a potentially more sensitive assessment of disc health. We determined the relationship between T2* relaxation time and proteoglycan content, collagen content, and compressive mechanics throughout the degenerative spectrum. Eighteen human cadaveric lumbar (L4–L5) discs were imaged using T2* MRI. The T2* relaxation time at five locations (nucleous pulposus or NP, anterior annulus fibrosis or AF, posterior AF, inner AF, and outer AF) was correlated with sulfated‐glycosaminoglycan (s‐GAG) content, hydroxyproline content, and residual stress and strain at each location. T2* relaxation times were significantly correlated with s‐GAG contents in all test locations and were particularly strong in the NP (r = 0.944; p < 0.001) and inner AF (r = 0.782; p < 0.001). T2* relaxation times were also significantly correlated with both residual stresses and excised strains in the NP (r = 0.857; p < 0.001: r = 0.816; p < 0.001), inner AF (r = 0.535; p = 0.022: r = 0.516; p = 0.028), and outer AF (r = 0.668; p = 0.002: r = 0.458; p = 0.041). These strong correlations highlight T2* MRI's ability to predict the biochemical and mechanical health of the disc. T2* MRI assessment of disc health is a clinically viable tool showing promise as a biomarker for distinguishing degenerative changes. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1083–1089, 2014.     

Exploring the Human Cytomegalovirus Core Nuclear Egress Complex as a Novel Antiviral Target: A New Type of Small Molecule Inhibitors

Nuclear egress is an essential process in the replication of human cytomegalovirus (HCMV), as it enables the migration of newly formed viral capsids from the nucleus into the cytoplasm. Inhibition of the HCMV core nuclear egress complex (core NEC), composed of viral proteins pUL50 and pUL53, has been proposed as a potential new target for the treatment of HCMV infection and disease. Here, we present a new type of small molecule inhibitors of HCMV core NEC formation, which inhibit the pUL50-pUL53 interaction at nanomolar concentrations. These inhibitors, i.e., verteporfin and merbromin, were identified through the screening of the Prestwick Chemical Library^® of approved drug compounds. The inhibitory effect of merbromin is both compound- and target-specific, as no inhibition was seen for other mercury-organic compounds. Furthermore, merbromin does not inhibit an unrelated protein–protein interaction either. More importantly, merbromin was found to inhibit HCMV infection of cells in three different assays, as well as to disrupt HCMV NEC nuclear rim formation. Thus, while not being an ideal drug candidate by itself, merbromin may serve as a blueprint for small molecules with high HCMV core NEC inhibitory potential, as candidates for novel anti-herpesviral drugs.     

Screening of Bacteriophage Encoded Toxic Proteins with a Next Generation Sequencing-Based Assay

Bacteriophage vB_EcoM_fHy-Eco03 (fHy-Eco03 for short) was isolated from a sewage sample based on its ability to infect an Escherichia coli clinical blood culture isolate. Altogether, 32 genes encoding hypothetical proteins of unknown function (HPUFs) were identified from the genomic sequence of fHy-Eco03. The HPUFs were screened for toxic properties (toxHPUFs) with a novel, Next Generation Sequencing (NGS)-based approach. This approach identifies toxHPUF-encoding genes through comparison of gene-specific read coverages in DNA from pooled ligation mixtures before electroporation and pooled transformants after electroporation. The performance and reliability of the NGS screening assay was compared with a plating efficiency-based method, and both methods identified the fHy-Eco03 gene g05 product as toxic. While the outcomes of the two screenings were highly similar, the NGS screening assay outperformed the plating efficiency assay in both reliability and efficiency. The NGS screening assay can be used as a high throughput method in the search for new phage-inspired antimicrobial molecules.     

Ultrastructural evaluation of postischemic cell death (lethal reperfusion injury) in porcine hearts

This study investigated whether reperfusion results in an increase of ultrastructurally determined myocardial injury in pig hearts. The left anterior descending coronary artery (LAD) was distally occluded in 12 pigs for 35–45 minutes and then reperfused for 3 hours. At the end of ischemia, as well as after 3 hours of reperfusion, one transmural biopsy was removed from the center of the risk region and subdivided into four specimens, representing the subendocardial (I), subendo-midmyocardial (II), subepi-midmyocardial (III), and subepicardial layers (IV). The degree of injury was assessed by electronmicroscopy and was scored as reversible (1), an almost equal mixture of reversible and irreversible (2), and totally irreversible (3) damage. In addition, infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic (dye technique) myocardium. Infarct sizes ranged from 29.3% to 93% (mean 61.2%). The scores of injury of the four tissue layers before and after reperfusion did not differ significantly: layer I, 2.4 ± 0.8/2.3 ± 0.9; layer II, 2.2 ± 0.9/2.0 ± 0.9; layer III, 1.8 ± 0.9/2.0 ± 0.9; and layer IV, 1.6 ± 0.9/1.3 ± 0.6. The means of the four layers were almost identical at the end of ischemia (2.1 ± 0.8) and after 3 hours of reperfusion (2.0 ± 0.6). A linear regression analysis with 95% confidence limits of the score values before and after reperfusion indicated that maximally 25% of a mean final infarct size of about 50% may be due to lethal reperfusion injury. This study suggests that cell death in regional ischemia and reperfusion occurs predominantly during ischemia and not during reperfusion.     

Pancreatic enzyme supplementation therapy

Opinion statement Effective treatment of malabsorption due to severe pancreatic exocrine insufficiency requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. To achieve this, modern therapeutic concepts recommend administration of 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres. In case of treatment failure, dosage should be increased two to three times. If this still is not successful, compliance may be checked by measurement of fecal chymotrypsin, although this is not a standardized procedure. In the compliant patient, diagnosis of pancreatic exocrine insufficiency needs to be reviewed, particularly cases of celiac disease, (concomitant) bacterial overgrowth, and blind loop syndrome, as well as giardiasis, which need to be excluded or otherwise be treated specifically. Finally, additional acid suppression with application of unprotected pancreatin and/or reduced fat intake may help to control malabsorption. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy. On the one hand, this leads to loss of energy that may only partly be compensated for by increased nutrient intake. On the other hand, increased nutrient exposition of distal intestinal sites may release excessive amounts of mostly inhibitory distal intestinal neurohumoral mediators, and thereby disturb gastrointestinal secretory and motor functions. Consequently, future developments are needed for optimizing treatment.